Advances in cutaneous squamous cell carcinoma.
Journal
Nature reviews. Cancer
ISSN: 1474-1768
Titre abrégé: Nat Rev Cancer
Pays: England
ID NLM: 101124168
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
accepted:
06
04
2023
medline:
28
6
2023
pubmed:
8
6
2023
entrez:
7
6
2023
Statut:
ppublish
Résumé
Human malignancies arise predominantly in tissues of epithelial origin, where the stepwise transformation from healthy epithelium to premalignant dysplasia to invasive neoplasia involves sequential dysregulation of biological networks that govern essential functions of epithelial homeostasis. Cutaneous squamous cell carcinoma (cSCC) is a prototype epithelial malignancy, often with a high tumour mutational burden. A plethora of risk genes, dominated by UV-induced sun damage, drive disease progression in conjunction with stromal interactions and local immunomodulation, enabling continuous tumour growth. Recent studies have identified subpopulations of SCC cells that specifically interact with the tumour microenvironment. These advances, along with increased knowledge of the impact of germline genetics and somatic mutations on cSCC development, have led to a greater appreciation of the complexity of skin cancer pathogenesis and have enabled progress in neoadjuvant immunotherapy, which has improved pathological complete response rates. Although measures for the prevention and therapeutic management of cSCC are associated with clinical benefit, the prognosis remains poor for advanced disease. Elucidating how the genetic mechanisms that drive cSCC interact with the tumour microenvironment is a current focus in efforts to understand, prevent and treat cSCC.
Identifiants
pubmed: 37286893
doi: 10.1038/s41568-023-00583-5
pii: 10.1038/s41568-023-00583-5
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
430-449Informations de copyright
© 2023. Springer Nature Limited.
Références
Chang, M. S., Azin, M. & Demehri, S. Cutaneous squamous cell carcinoma: the frontier of cancer immunoprevention. Annu. Rev. Pathol. 17, 101–119 (2022).
pubmed: 35073167
doi: 10.1146/annurev-pathol-042320-120056
Rogers, H. W., Weinstock, M. A., Feldman, S. R. & Coldiron, B. M. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol. 151, 1081–1086 (2015).
pubmed: 25928283
doi: 10.1001/jamadermatol.2015.1187
Qureshi, A. A., Laden, F., Colditz, G. A. & Hunter, D. J. Geographic variation and risk of skin cancer in US women. Differences between melanoma, squamous cell carcinoma, and basal cell carcinoma. Arch. Intern. Med. 168, 501–507 (2008).
pubmed: 18332296
doi: 10.1001/archinte.168.5.501
Dusendang, J. R. et al. Cohort and nested case-control study of cutaneous squamous cell carcinoma in solid organ transplant recipients, by medication. J. Am. Acad. Dermatol. 86, 598–606 (2022).
pubmed: 34384835
doi: 10.1016/j.jaad.2021.07.065
Nadhan, K. S. et al. Risk factors for keratinocyte carcinoma skin cancer in nonwhite individuals: a retrospective analysis. J. Am. Acad. Dermatol. 81, 373–378 (2019).
pubmed: 30703457
doi: 10.1016/j.jaad.2019.01.038
Nehal, K. S. & Bichakjian, C. K. Update on keratinocyte carcinomas. N. Engl. J. Med. 379, 363–374 (2018).
pubmed: 30044931
doi: 10.1056/NEJMra1708701
Que, S. K. T., Zwald, F. O. & Schmults, C. D. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J. Am. Acad. Dermatol. 78, 237–247 (2018).
doi: 10.1016/j.jaad.2017.08.059
Thompson, A. K., Kelley, B. F., Prokop, L. J., Murad, M. H. & Baum, C. L. Risk factors for cutaneous squamous cell carcinoma recurrence, metastasis, and disease-specific death: a systematic review and meta-analysis. JAMA Dermatol. 152, 419–428 (2016).
pubmed: 26762219
pmcid: 4833641
doi: 10.1001/jamadermatol.2015.4994
Haisma, M. S. et al. Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. J. Am. Acad. Dermatol. 75, 722–730 (2016).
doi: 10.1016/j.jaad.2016.06.010
Eigentler, T. K. et al. Survival of patients with cutaneous squamous cell carcinoma: results of a prospective cohort study. J. Invest. Dermatol. 137, 2309–2315 (2017).
pubmed: 28736229
doi: 10.1016/j.jid.2017.06.025
Schmults, C. D., Karia, P. S., Carter, J. B., Han, J. & Qureshi, A. A. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. 149, 541–547 (2013).
pubmed: 23677079
doi: 10.1001/jamadermatol.2013.2139
Eviston, T. J. et al. Gene expression profiling of perineural invasion in head and neck cutaneous squamous cell carcinoma. Sci. Rep. 11, 13192 (2021).
pubmed: 34162930
pmcid: 8222302
doi: 10.1038/s41598-021-92335-4
Venables, Z. C. et al. Nationwide incidence of metastatic cutaneous squamous cell carcinoma in england. JAMA Dermatol. 155, 298–306 (2019).
pubmed: 30484823
doi: 10.1001/jamadermatol.2018.4219
Karia, P. S., Han, J. & Schmults, C. D. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J. Am. Acad. Dermatol. 68, 957–966 (2013).
pubmed: 23375456
doi: 10.1016/j.jaad.2012.11.037
Pickering, C. R. et al. Mutational landscape of aggressive cutaneous squamous cell carcinoma. Clin. Cancer Res. 20, 6582–6592 (2014).
pubmed: 25303977
pmcid: 4367811
doi: 10.1158/1078-0432.CCR-14-1768
Cammareri, P. et al. Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma. Nat. Commun. 7, 12493 (2016).
pubmed: 27558455
pmcid: 5007296
doi: 10.1038/ncomms12493
Inman, G. J. et al. The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature. Nat. Commun. 9, 3667 (2018).
pubmed: 30202019
pmcid: 6131170
doi: 10.1038/s41467-018-06027-1
Rodriguez-Paredes, M. et al. Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin. Nat. Commun. 9, 577 (2018).
pubmed: 29422656
pmcid: 5805678
doi: 10.1038/s41467-018-03025-1
Ji, A. L. et al. Multimodal analysis of composition and spatial architecture in human squamous cell carcinoma. Cell 182, 497–514 e422 (2020). Using cSCC as a model, this paper integrates single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging, revealing a complex interplay of malignant and nonmalignant cells at the tumour edge, and outlines a tumour-specific cell type at the leading edge that may drive stromal and immune changes that facilitate progression.
pubmed: 32579974
pmcid: 7391009
doi: 10.1016/j.cell.2020.05.039
Oshimori, N., Oristian, D. & Fuchs, E. TGF-β promotes heterogeneity and drug resistance in squamous. Cell Carcinoma Cell 160, 963–976 (2015). This study shows how TGFβ directly interacts with tumour cells to promote tumour heterogeneity and implicates this pathway in drug-resistance mechanisms.
pubmed: 25723170
Manyam, B. V. et al. A multi-institutional comparison of outcomes of immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for cutaneous squamous cell carcinoma of the head and neck. Cancer 123, 2054–2060 (2017).
pubmed: 28171708
doi: 10.1002/cncr.30601
Gross, N. D. et al. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. N. Engl. J. Med. 387, 1557–1568 (2022). Landmark paper demonstrating the efficacy of immunotherapy with cemiplimab for cSCC in a phase II trial.
pubmed: 36094839
pmcid: 9844515
doi: 10.1056/NEJMoa2209813
Agbai, O. N. et al. Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. J. Am. Acad. Dermatol. 70, 748–762 (2014).
pubmed: 24485530
doi: 10.1016/j.jaad.2013.11.038
Tadokoro, T. et al. UV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin. FASEB J. 17, 1177–1179 (2003).
pubmed: 12692083
doi: 10.1096/fj.02-0865fje
Thody, A. J. et al. Pheomelanin as well as eumelanin is present in human epidermis. J. Invest. Dermatol. 97, 340–344 (1991).
pubmed: 2071942
doi: 10.1111/1523-1747.ep12480680
Hunt, G. et al. Eumelanin and phaeomelanin contents of human epidermis and cultured melanocytes. Pigment. Cell Res. 8, 202–208 (1995).
pubmed: 8610071
doi: 10.1111/j.1600-0749.1995.tb00664.x
Ziegler, A. et al. Sunburn and p53 in the onset of skin cancer. Nature 372, 773–776 (1994). This study identifies the role of UVR in both tumour initiation and tumour propagation through p53.
pubmed: 7997263
doi: 10.1038/372773a0
Xu, X. et al. HSD17B7 gene in self-renewal and oncogenicity of keratinocytes from Black versus White populations. EMBO Mol. Med. 13, e14133 (2021).
pubmed: 34185380
pmcid: 8261506
doi: 10.15252/emmm.202114133
Martena, M. J. et al. Monitoring of mercury, arsenic, and lead in traditional Asian herbal preparations on the Dutch market and estimation of associated risks. Food Addit. Contam. Part. A Chem. Anal. Control. Expo. Risk Assess. 27, 190–205 (2010).
pubmed: 19890755
doi: 10.1080/02652030903207235
Oh, C. C., Jin, A. & Koh, W. P. Trends of cutaneous basal cell carcinoma, squamous cell carcinoma, and melanoma among the Chinese, Malays, and Indians in Singapore from 1968-2016. JAAD Int. 4, 39–45 (2021).
pmcid: 8361884
doi: 10.1016/j.jdin.2021.05.006
Knobeloch, L. M., Zierold, K. M. & Anderson, H. A. Association of arsenic-contaminated drinking-water with prevalence of skin cancer in Wisconsin’s Fox River Valley. J. Health Popul. Nutr. 24, 206–213 (2006).
Karagas, M. R., Gossai, A., Pierce, B. & Ahsan, H. Drinking water arsenic contamination, skin lesions, and malignancies: a systematic review of the global evidence. Curr. Env. Health Rep. 2, 52–68 (2015).
doi: 10.1007/s40572-014-0040-x
Gronskov, K., Ek, J. & Brondum-Nielsen, K. Oculocutaneous albinism. Orphanet J. Rare Dis. 2, 43 (2007).
pubmed: 17980020
pmcid: 2211462
doi: 10.1186/1750-1172-2-43
Fine, J. D., Johnson, L. B., Weiner, M., Li, K. P. & Suchindran, C. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J. Am. Acad. Dermatol. 60, 203–211 (2009).
pubmed: 19026465
doi: 10.1016/j.jaad.2008.09.035
McGrath, J. A., Schofield, O. M., Mayou, B. J., McKee, P. H. & Eady, R. A. Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases. J. Cutan. Pathol. 19, 116–123 (1992).
pubmed: 1597567
doi: 10.1111/j.1600-0560.1992.tb01352.x
Ng, Y. Z. et al. Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa. Cancer Res. 72, 3522–3534 (2012).
pubmed: 22564523
doi: 10.1158/0008-5472.CAN-11-2996
Cho, R. J. et al. APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa. Sci. Transl. Med. 10, eaas9668 (2018).
pubmed: 30135250
doi: 10.1126/scitranslmed.aas9668
Youssefian, L., Vahidnezhad, H. & Uitto, J. Kindler syndrome. in GeneReviews (eds Adam, M. P. et al.) (University of Washington, 1993).
Siegel, D. H. et al. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. Am. J. Hum. Genet. 73, 174–187 (2003).
pubmed: 12789646
pmcid: 1180579
doi: 10.1086/376609
Rognoni, E. et al. Kindlin-1 controls Wnt and TGF-β availability to regulate cutaneous stem cell proliferation. Nat. Med. 20, 350–359 (2014).
pmcid: 3982140
doi: 10.1038/nm.3490
Chacon-Solano, E. et al. Fibroblast activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses. Br. J. Dermatol. 181, 512–522 (2019).
pmcid: 6850467
doi: 10.1111/bjd.17698
Sarin, K. Y. et al. Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma. Nat. Commun. 11, 820 (2020).
pmcid: 7010741
doi: 10.1038/s41467-020-14594-5
Kim, Y. et al. Genome-wide association study of actinic keratosis identifies new susceptibility loci implicated in pigmentation and immune regulation pathways. Commun. Biol. 5, 386 (2022).
pmcid: 9023580
doi: 10.1038/s42003-022-03301-3
Chahal, H. S. et al. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma. Nat. Commun. 7, 12048 (2016).
pmcid: 4960294
doi: 10.1038/ncomms12048
D’Orazio, J., Jarrett, S., Amaro-Ortiz, A. & Scott, T. UV radiation and the skin. Int. J. Mol. Sci. 14, 12222–12248 (2013).
pmcid: 3709783
doi: 10.3390/ijms140612222
Kim, Y. & He, Y. Y. Ultraviolet radiation-induced non-melanoma skin cancer: regulation of DNA damage repair and inflammation. Genes. Dis. 1, 188–198 (2014).
pmcid: 4307792
doi: 10.1016/j.gendis.2014.08.005
Vogeley, C., Rolfes, K. M., Krutmann, J. & Haarmann-Stemmann, T. The aryl hydrocarbon receptor in the pathogenesis of environmentally-induced squamous cell carcinomas of the skin. Front. Oncol. 12, 841721 (2022).
pmcid: 8927079
doi: 10.3389/fonc.2022.841721
Green, A. C. & Olsen, C. M. Cutaneous squamous cell carcinoma: an epidemiological review. Br. J. Dermatol. 177, 373–381 (2017).
doi: 10.1111/bjd.15324
Dotto, G. P. & Rustgi, A. K. Squamous cell cancers: a unified perspective on biology and genetics. Cancer Cell 29, 622–637 (2016).
pmcid: 4870309
doi: 10.1016/j.ccell.2016.04.004
Slaughter, D. P., Southwick, H. W. & Smejkal, W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6, 963–968 (1953). Landmark paper from 1953 introducing the concept of field cancerization, based on the observations of frequent arisal of tumours within the same area of tissue.
doi: 10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q
Martincorena, I. et al. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880–886 (2015). Seminal paper describing how somatic mutations linked to epithelial cancer exist in normal-appearing sun-exposed skin.
pubmed: 25999502
pmcid: 4471149
doi: 10.1126/science.aaa6806
Dotto, G. P. Multifocal epithelial tumors and field cancerization: stroma as a primary determinant. J. Clin. Invest. 124, 1446–1453 (2014).
pmcid: 3973113
doi: 10.1172/JCI72589
Hu, B. et al. Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling. Cell 149, 1207–1220 (2012). This study shows how mesenchymal NOTCH–CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumours, and in human skin inducable by UVR.
pmcid: 3578441
doi: 10.1016/j.cell.2012.03.048
Fisher, G. J. et al. Pathophysiology of premature skin aging induced by ultraviolet light. N. Engl. J. Med. 337, 1419–1428 (1997).
doi: 10.1056/NEJM199711133372003
Vosseler, S. et al. Distinct progression-associated expression of tumor and stromal MMPs in HaCaT skin SCCs correlates with onset of invasion. Int. J. Cancer 125, 2296–2306 (2009).
doi: 10.1002/ijc.24589
Lee, C. S. et al. Mutant collagen COL11A1 enhances cancerous invasion. Oncogene 40, 6299–6307 (2021).
pmcid: 8566234
doi: 10.1038/s41388-021-02013-y
Quan, T., He, T., Voorhees, J. J. & Fisher, G. J. Ultraviolet irradiation induces Smad7 via induction of transcription factor AP-1 in human skin fibroblasts. J. Biol. Chem. 280, 8079–8085 (2005).
doi: 10.1074/jbc.M409647200
Quan, T., He, T., Kang, S., Voorhees, J. J. & Fisher, G. J. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-β type II receptor/Smad signaling. Am. J. Pathol. 165, 741–751 (2004).
pmcid: 1618600
doi: 10.1016/S0002-9440(10)63337-8
Kripke, M. L. & Fisher, M. S. Immunologic parameters of ultraviolet carcinogenesis. J. Natl Cancer Inst. 57, 211–215 (1976).
doi: 10.1093/jnci/57.1.211
Simon, J. C., Tigelaar, R. E., Bergstresser, P. R., Edelbaum, D. & Cruz, P. D. Jr. Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4
pubmed: 1670944
doi: 10.4049/jimmunol.146.2.485
Loser, K. et al. IL-10 controls ultraviolet-induced carcinogenesis in mice. J. Immunol. 179, 365–371 (2007). This paper demonstrates how the immunosuppressive cytokine IL-10 dictates UVR-induced carcinogenesis in mouse skin.
pubmed: 17579057
doi: 10.4049/jimmunol.179.1.365
Bottomley, M. J., Thomson, J., Harwood, C. & Leigh, I. The role of the immune system in cutaneous squamous cell carcinoma. Int. J. Mol. Sci. 20, 2009 (2019).
pubmed: 31022866
pmcid: 6515307
doi: 10.3390/ijms20082009
Garssen, J. et al. UVB exposure-induced systemic modulation of Th1- and Th2-mediated immune responses. Immunology 97, 506–514 (1999).
pubmed: 10447774
pmcid: 2326852
doi: 10.1046/j.1365-2567.1999.00801.x
Jantschitsch, C., Weichenthal, M., Proksch, E., Schwarz, T. & Schwarz, A. IL-12 and IL-23 affect photocarcinogenesis differently. J. Invest. Dermatol. 132, 1479–1486 (2012).
pubmed: 22297634
doi: 10.1038/jid.2011.469
Maeda, A. et al. Enhanced photocarcinogenesis in interleukin-12-deficient mice. Cancer Res. 66, 2962–2969 (2006).
pubmed: 16540644
doi: 10.1158/0008-5472.CAN-05-3614
Nasti, T. H. et al. Differential roles of T-cell subsets in regulation of ultraviolet radiation induced cutaneous photocarcinogenesis. Photochem. Photobiol. 87, 387–398 (2011).
pubmed: 21143237
doi: 10.1111/j.1751-1097.2010.00859.x
Lewis, J. M. et al. Chronic UV radiation-induced RORγt
doi: 10.1073/pnas.2016963118
pubmed: 34903653
pmcid: 8713797
Azzimonti, B. et al. Intense Foxp3
pubmed: 24910265
doi: 10.1111/bjd.13172
Bluth, M. J. et al. Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation. J. Invest. Dermatol. 129, 2451–2462 (2009).
pmcid: 2846605
doi: 10.1038/jid.2009.96
Armstrong, B. K. & Kricker, A. The epidemiology of UV induced skin cancer. J. Photochem. Photobiol. B 63, 8–18 (2001).
pubmed: 11684447
doi: 10.1016/S1011-1344(01)00198-1
Schmitt, J., Seidler, A., Diepgen, T. L. & Bauer, A. Occupational ultraviolet light exposure increases the risk for the development of cutaneous squamous cell carcinoma: a systematic review and meta-analysis. Br. J. Dermatol. 164, 291–307 (2011).
pubmed: 21054335
doi: 10.1111/j.1365-2133.2010.10118.x
Alfonso, J. H. et al. Occupation and relative risk of cutaneous squamous cell carcinoma (cSCC): a 45-year follow-up study in 4 Nordic countries. J. Am. Acad. Dermatol. 75, 548–555 (2016).
pubmed: 27262759
doi: 10.1016/j.jaad.2016.03.033
Garrett, G. L. et al. Incidence of and risk factors for skin cancer in organ transplant recipients in the United States. JAMA Dermatol. 153, 296–303 (2017).
pubmed: 28097368
doi: 10.1001/jamadermatol.2016.4920
Krynitz, B. et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008–a Swedish population-based study. Int. J. Cancer 132, 1429–1438 (2013).
pubmed: 22886725
doi: 10.1002/ijc.27765
Falchi, L. et al. Incidence and prognostic impact of other cancers in a population of long-term survivors of chronic lymphocytic leukemia. Ann. Oncol. 27, 1100–1106 (2016).
pubmed: 26912560
pmcid: 4880062
doi: 10.1093/annonc/mdw072
Silverberg, M. J. et al. HIV infection status, immunodeficiency, and the incidence of non-melanoma skin cancer. J. Natl Cancer Inst. 105, 350–360 (2013).
pubmed: 23291375
pmcid: 3589255
doi: 10.1093/jnci/djs529
Nguyen, P., Vin-Christian, K., Ming, M. E. & Berger, T. Aggressive squamous cell carcinomas in persons infected with the human immunodeficiency virus. Arch. Dermatol. 138, 758–763 (2002).
pubmed: 12056956
doi: 10.1001/archderm.138.6.758
Azzimonti, B. et al. CD8+ T-cell lymphocytopenia and lack of EVER mutations in a patient with clinically and virologically typical epidermodysplasia verruciformis. Arch. Dermatol. 141, 1323–1325 (2005).
pubmed: 16230580
Zavattaro, E. et al. Identification of defective Fas function and variation of the perforin gene in an epidermodysplasia verruciformis patient lacking EVER1 and EVER2 mutations. J. Invest. Dermatol. 128, 732–735 (2008).
pubmed: 17960179
doi: 10.1038/sj.jid.5701124
Landini, M. M. et al. α- and β-Papillomavirus infection in a young patient with an unclassified primary T-cell immunodeficiency and multiple mucosal and cutaneous lesions. J. Am. Acad. Dermatol. 71, 108–115 e101 (2014).
doi: 10.1016/j.jaad.2014.01.859
Wang, J., Aldabagh, B., Yu, J. & Arron, S. T. Role of human papillomavirus in cutaneous squamous cell carcinoma: a meta-analysis. J. Am. Acad. Dermatol. 70, 621–629 (2014).
pmcid: 3959664
doi: 10.1016/j.jaad.2014.01.857
Bernard, H. U. et al. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 401, 70–79 (2010).
doi: 10.1016/j.virol.2010.02.002
Arron, S. T., Ruby, J. G., Dybbro, E., Ganem, D. & Derisi, J. L. Transcriptome sequencing demonstrates that human papillomavirus is not active in cutaneous squamous cell carcinoma. J. Invest. Dermatol. 131, 1745–1753 (2011).
pmcid: 3136639
doi: 10.1038/jid.2011.91
Hazard, K. et al. Cutaneous human papillomaviruses persist on healthy skin. J. Invest. Dermatol. 127, 116–119 (2007).
doi: 10.1038/sj.jid.5700570
Middleton, K. et al. Organization of human papillomavirus productive cycle during neoplastic progression provides a basis for selection of diagnostic markers. J. Virol. 77, 10186–10201 (2003).
pmcid: 228472
doi: 10.1128/JVI.77.19.10186-10201.2003
Bosch, F. X. et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J. Natl Cancer Inst. 87, 796–802 (1995).
doi: 10.1093/jnci/87.11.796
Riddel, C., Rashid, R. & Thomas, V. Ungual and periungual human papillomavirus-associated squamous cell carcinoma: a review. J. Am. Acad. Dermatol. 64, 1147–1153 (2011).
doi: 10.1016/j.jaad.2010.02.057
Munger, K., Phelps, W. C., Bubb, V., Howley, P. M. & Schlegel, R. The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J. Virol. 63, 4417–4421 (1989).
pmcid: 251060
doi: 10.1128/jvi.63.10.4417-4421.1989
Hawley-Nelson, P., Vousden, K. H., Hubbert, N. L., Lowy, D. R. & Schiller, J. T. HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J. 8, 3905–3910 (1989).
pmcid: 402081
doi: 10.1002/j.1460-2075.1989.tb08570.x
Huibregtse, J. M., Scheffner, M. & Howley, P. M. A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J. 10, 4129–4135 (1991).
pmcid: 453163
doi: 10.1002/j.1460-2075.1991.tb04990.x
Dyson, N., Howley, P. M., Munger, K. & Harlow, E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243, 934–937 (1989). Seminal paper demonstrating how the E7 oncoprotein from HPV16 regulates retinoblastoma signalling.
doi: 10.1126/science.2537532
de Sanjose, S. et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 11, 1048–1056 (2010).
doi: 10.1016/S1470-2045(10)70230-8
Mirabello, L. et al. HPV16 E7 genetic conservation is critical to carcinogenesis. Cell 170, 1164–1174 e1166 (2017).
pmcid: 5674785
doi: 10.1016/j.cell.2017.08.001
Viarisio, D. et al. Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice. PLoS Pathog. 14, e1006783 (2018).
pmcid: 5764406
doi: 10.1371/journal.ppat.1006783
Barbosa, M. S., Vass, W. C., Lowy, D. R. & Schiller, J. T. In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential. J. Virol. 65, 292–298 (1991).
pmcid: 240516
doi: 10.1128/jvi.65.1.292-298.1991
Asgari, M. M. et al. Detection of human papillomavirus DNA in cutaneous squamous cell carcinoma among immunocompetent individuals. J. Invest. Dermatol. 128, 1409–1417 (2008).
pmcid: 3268673
doi: 10.1038/sj.jid.5701227
Strickley, J. D. et al. Immunity to commensal papillomaviruses protects against skin cancer. Nature 575, 519–522 (2019). Thought-provoking paper demonstrating how commensal viruses could prevent development of skin cancer by boosting immunity.
pmcid: 6872936
doi: 10.1038/s41586-019-1719-9
Herman, M. et al. Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients. J. Lab. Clin. Med. 137, 14–20 (2001).
doi: 10.1067/mlc.2001.111469
McCarroll, N. et al. An evaluation of the mode of action framework for mutagenic carcinogens case study: cyclophosphamide. Env. Mol. Mutagen. 49, 117–131 (2008).
doi: 10.1002/em.20372
Lin, J. Q. et al. A 10-year retrospective cohort study of ruxolitinib and association with nonmelanoma skin cancer in patients with polycythemia vera and myelofibrosis. J. Am. Acad. Dermatol. 86, 339–344 (2022).
pubmed: 34648874
doi: 10.1016/j.jaad.2021.10.004
De Simone, C. et al. Multiple squamous cell carcinomas of the skin during long-term treatment with hydroxyurea. Eur. J. Dermatol. 8, 114–115 (1998).
pubmed: 9649662
Ming, M., Zhao, B., Qiang, L. & He, Y. Y. Effect of immunosuppressants tacrolimus and mycophenolate mofetil on the keratinocyte UVB response. Photochem. Photobiol. 91, 242–247 (2015).
pubmed: 25039758
doi: 10.1111/php.12318
Euvrard, S. et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N. Engl. J. Med. 367, 329–339 (2012).
pubmed: 22830463
doi: 10.1056/NEJMoa1204166
Hojo, M. et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 397, 530–534 (1999).
pubmed: 10028970
doi: 10.1038/17401
Maluccio, M. et al. Tacrolimus enhances transforming growth factor-beta1 expression and promotes tumor progression. Transplantation 76, 597–602 (2003).
pubmed: 12923450
doi: 10.1097/01.TP.0000081399.75231.3B
Guba, M., Graeb, C., Jauch, K. W. & Geissler, E. K. Pro- and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation 77, 1777–1782 (2004).
pubmed: 15223891
doi: 10.1097/01.TP.0000120181.89206.54
Wu, X. et al. Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 465, 368–372 (2010).
pubmed: 20485437
pmcid: 3050632
doi: 10.1038/nature08996
Shin, D. et al. Association between the use of thiazide diuretics and the risk of skin cancers: a meta-analysis of observational studies. J. Clin. Med. Res. 11, 247–255 (2019).
pubmed: 30937114
pmcid: 6436572
doi: 10.14740/jocmr3744
Selvaag, E., Petersen, A. B., Gniadecki, R., Thorn, T. & Wulf, H. C. Phototoxicity to diuretics and antidiabetics in the cultured keratinocyte cell line HaCaT: evaluation by clonogenic assay and single cell gel electrophoresis Comet assay. Photodermatol. Photoimmunol. Photomed. 18, 90–95 (2002).
pubmed: 12147042
doi: 10.1034/j.1600-0781.2002.180206.x
O’Donovan, P. et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 309, 1871–1874 (2005).
pubmed: 16166520
pmcid: 2426755
doi: 10.1126/science.1114233
Karran, P. & Brem, R. Protein oxidation, UVA and human DNA repair. DNA Repair 44, 178–185 (2016).
pubmed: 27324272
pmcid: 4962777
doi: 10.1016/j.dnarep.2016.05.024
Williams, K., Mansh, M., Chin-Hong, P., Singer, J. & Arron, S. T. Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin. Infect. Dis. 58, 997–1002 (2014).
pubmed: 24363331
doi: 10.1093/cid/cit940
McCarthy, K. L., Playford, E. G., Looke, D. F. & Whitby, M. Severe photosensitivity causing multifocal squamous cell carcinomas secondary to prolonged voriconazole therapy. Clin. Infect. Dis. 44, e55–e56 (2007).
pubmed: 17278050
doi: 10.1086/511685
Cowen, E. W. et al. Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole. J. Am. Acad. Dermatol. 62, 31–37 (2010).
pubmed: 19896749
doi: 10.1016/j.jaad.2009.09.033
Hamandi, B. et al. Voriconazole and squamous cell carcinoma after lung transplantation: a multicenter study. Am. J. Transplant. 18, 113–124 (2018).
pubmed: 28898527
doi: 10.1111/ajt.14500
Tang, H., Shi, W., Song, Y. & Han, J. Voriconazole exposure and risk of cutaneous squamous cell carcinoma among lung or hematopoietic cell transplant patients: a systematic review and meta-analysis. J. Am. Acad. Dermatol. 80, 500–507 e510 (2019).
pubmed: 30130598
doi: 10.1016/j.jaad.2018.08.010
D’Arcy, M. E. et al. Voriconazole and the risk of keratinocyte carcinomas among lung transplant recipients in the United States. JAMA Dermatol. 156, 772–779 (2020).
pubmed: 32401271
doi: 10.1001/jamadermatol.2020.1141
Ikeya, S., Sakabe, J. I., Yamada, T., Naito, T. & Tokura, Y. Voriconazole-induced photocarcinogenesis is promoted by aryl hydrocarbon receptor-dependent COX-2 upregulation. Sci. Rep. 8, 5050 (2018).
pubmed: 29568008
pmcid: 5864729
doi: 10.1038/s41598-018-23439-7
Anforth, R. M. et al. Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma. Br. J. Dermatol. 167, 1153–1160 (2012).
pubmed: 22804352
doi: 10.1111/j.1365-2133.2012.11155.x
Lacouture, M. E. et al. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist 18, 314–322 (2013).
pubmed: 23457002
pmcid: 3607529
doi: 10.1634/theoncologist.2012-0333
Flaherty, K. T. et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N. Engl. J. Med. 367, 1694–1703 (2012).
pubmed: 23020132
pmcid: 3549295
doi: 10.1056/NEJMoa1210093
Robert, C. et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med. 372, 30–39 (2015).
pubmed: 25399551
doi: 10.1056/NEJMoa1412690
Pott, P. Chirurgical Observations Relative to the Cataract, the Polypus of the Nose, Cancer of the Scrotum, Different Kinds of Ruptures, and the Mortification of the Toes and Feet (printed by T. J. Carnegy, for L. Hawes, W. Clarke and R. Collins, 1775).
Siddens, L. K. et al. Polycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse. Toxicol. Appl. Pharmacol. 264, 377–386 (2012).
pubmed: 22935520
pmcid: 3483092
doi: 10.1016/j.taap.2012.08.014
De Hertog, S. A. et al. Relation between smoking and skin cancer. J. Clin. Oncol. 19, 231–238 (2001).
doi: 10.1200/JCO.2001.19.1.231
Braithwaite, E., Wu, X. & Wang, Z. Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts: involvement of two excision repair mechanisms in vitro. Carcinogenesis 19, 1239–1246 (1998).
pubmed: 9683183
doi: 10.1093/carcin/19.7.1239
Shimizu, Y. et al. Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc. Natl Acad. Sci. USA 97, 779–782 (2000).
pubmed: 10639156
pmcid: 15407
doi: 10.1073/pnas.97.2.779
Hahn, M. E., Karchner, S. I., Shapiro, M. A. & Perera, S. A. Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family. Proc. Natl Acad. Sci. USA 94, 13743–13748 (1997).
pubmed: 9391097
pmcid: 28377
doi: 10.1073/pnas.94.25.13743
Pollet, M. et al. The AHR represses nucleotide excision repair and apoptosis and contributes to UV-induced skin carcinogenesis. Cell Death Differ. 25, 1823–1836 (2018).
pubmed: 30013037
pmcid: 6180092
doi: 10.1038/s41418-018-0160-1
Luch, A. Nature and nurture — lessons from chemical carcinogenesis. Nat. Rev. Cancer 5, 113–125 (2005).
pubmed: 15660110
doi: 10.1038/nrc1546
Yu, H. S., Liao, W. T. & Chai, C. Y. Arsenic carcinogenesis in the skin. J. Biomed. Sci. 13, 657–666 (2006).
pubmed: 16807664
doi: 10.1007/s11373-006-9092-8
Czarnecki, D., Meehan, C. J., Bruce, F. & Culjak, G. The majority of cutaneous squamous cell carcinomas arise in actinic keratoses. J. Cutan. Med. Surg. 6, 207–209 (2002).
pubmed: 11951126
doi: 10.1177/120347540200600301
Marks, R., Rennie, G. & Selwood, T. S. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1, 795–797 (1988).
pubmed: 2895318
doi: 10.1016/S0140-6736(88)91658-3
Reinehr, C. P. H. & Bakos, R. M. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. Bras. Dermatol. 94, 637–657 (2019).
doi: 10.1016/j.abd.2019.10.004
Criscione, V. D. et al. Actinic keratoses: natural history and risk of malignant transformation in the veterans affairs topical tretinoin chemoprevention trial. Cancer 115, 2523–2530 (2009).
pubmed: 19382202
doi: 10.1002/cncr.24284
Cassarino, D. S., Derienzo, D. P. & Barr, R. J. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one. J. Cutan. Pathol. 33, 191–206 (2006).
pubmed: 16466506
Willenbrink, T. J. et al. Field cancerization: definition, epidemiology, risk factors, and outcomes. J. Am. Acad. Dermatol. 83, 709–717 (2020).
pubmed: 32387665
doi: 10.1016/j.jaad.2020.03.126
Waldman, A. & Schmults, C. Cutaneous squamous cell carcinoma. Hematol. Oncol. Clin. North Am. 33, 1–12 (2019).
pubmed: 30497667
doi: 10.1016/j.hoc.2018.08.001
Pandeya, N., Olsen, C. M. & Whiteman, D. C. The incidence and multiplicity rates of keratinocyte cancers in Australia. Med. J. Aust. 207, 339–343 (2017).
pubmed: 29020905
doi: 10.5694/mja17.00284
Morton, S. & Muir, J. Field cancerization in the skin: past errors repeated. J. Am. Acad. Dermatol. 85, e41 (2021).
pubmed: 33711362
doi: 10.1016/j.jaad.2020.12.094
Pitha-Rowe, I., Petty, W. J., Kitareewan, S. & Dmitrovsky, E. Retinoid target genes in acute promyelocytic leukemia. Leukemia 17, 1723–1730 (2003).
pubmed: 12970771
doi: 10.1038/sj.leu.2403065
Lebwohl, M., Tannis, C. & Carrasco, D. Acitretin suppression of squamous cell carcinoma: case report and literature review. J. Dermatol. Treat. 14, 3–6 (2003).
doi: 10.1080/jdt.14.s2.3.6
Kraemer, K. H., DiGiovanna, J. J., Moshell, A. N., Tarone, R. E. & Peck, G. L. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N. Engl. J. Med. 318, 1633–1637 (1988).
pubmed: 3287161
doi: 10.1056/NEJM198806233182501
Bavinck, J. N. et al. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J. Clin. Oncol. 13, 1933–1938 (1995).
pubmed: 7636533
doi: 10.1200/JCO.1995.13.8.1933
Driessens, G., Beck, B., Caauwe, A., Simons, B. D. & Blanpain, C. Defining the mode of tumour growth by clonal analysis. Nature 488, 527–530 (2012). A central study presenting experimental evidence for the existence of cancer stem cells during unperturbed solid tumour growth by clonal analysis of squamous skin tumours using genetic lineage tracing.
pubmed: 22854777
pmcid: 5553110
doi: 10.1038/nature11344
Latil, M. et al. Cell-type-specific chromatin states differentially prime squamous cell carcinoma tumor-initiating cells for epithelial to mesenchymal transition. Cell Stem Cell 20, 191–204.e195 (2017).
pubmed: 27889319
doi: 10.1016/j.stem.2016.10.018
Sánchez-Danés, A. & Blanpain, C. Deciphering the cells of origin of squamous cell carcinomas. Nat. Rev. Cancer 18, 549–561 (2018).
pubmed: 29849070
pmcid: 7170720
doi: 10.1038/s41568-018-0024-5
Di Nardo, L. et al. Molecular genetics of cutaneous squamous cell carcinoma: perspective for treatment strategies. J. Eur. Acad. Dermatol. Venereol. 34, 932–941 (2020).
pubmed: 31747091
doi: 10.1111/jdv.16098
Wang, N. J. et al. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc. Natl Acad. Sci. USA 108, 17761–17766 (2011). Paper identifying NOTCH1 and NOTCH2 mutations in a majority of cSCCs.
pubmed: 22006338
pmcid: 3203814
doi: 10.1073/pnas.1114669108
Pacella, G. & Capell, B. C. Epigenetic and metabolic interplay in cutaneous squamous cell carcinoma. Exp. Dermatol. 30, 1115–1125 (2021).
pubmed: 33844325
pmcid: 8324523
doi: 10.1111/exd.14354
Lee, C. S. et al. Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma. Nat. Genet. 46, 1060–1062 (2014).
pubmed: 25194279
pmcid: 4324615
doi: 10.1038/ng.3091
South, A. P. et al. NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis. J. Investig. Dermatol. 134, 2630–2638 (2014).
pubmed: 24662767
doi: 10.1038/jid.2014.154
Li, Y. Y. et al. Genomic analysis of metastatic cutaneous squamous cell carcinoma. Clin. Cancer Res. 21, 1447–1456 (2015).
pubmed: 25589618
pmcid: 4359951
doi: 10.1158/1078-0432.CCR-14-1773
Ratushny, V., Gober, M. D., Hick, R., Ridky, T. W. & Seykora, J. T. From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. J. Clin. Invest. 122, 464–472 (2012).
pubmed: 22293185
pmcid: 3266779
doi: 10.1172/JCI57415
Tufaro, A. P. et al. Molecular markers in cutaneous squamous cell carcinoma. Int. J. Surg. Oncol. 2011, 231475 (2011).
pubmed: 22312497
pmcid: 3265276
Nassar, D., Latil, M., Boeckx, B., Lambrechts, D. & Blanpain, C. Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma. Nat. Med. 21, 946–954 (2015). A comprehensive analysis of DMBA-induced skin cancer.
pubmed: 26168291
doi: 10.1038/nm.3878
Huang, P. Y. & Balmain, A. Modeling cutaneous squamous carcinoma development in the mouse. Cold Spring Harb. Perspect. Med. 4, a013623 (2014).
pubmed: 25183851
pmcid: 4143107
doi: 10.1101/cshperspect.a013623
Balmain, A. & Pragnell, I. B. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature 303, 72–74 (1983). Seminal paper showing that mouse cSCCs induced by chemical carcinogens contain a Hras oncogene.
pubmed: 6843661
doi: 10.1038/303072a0
Morris, R. J., Fischer, S. M. & Slaga, T. J. Evidence that a slowly cycling subpopulation of adult murine epidermal cells retains carcinogen. Cancer Res. 46, 3061–3066 (1986).
pubmed: 3698024
Furstenberger, G. et al. Stimulatory role of transforming growth factors in multistage skin carcinogenesis: possible explanation for the tumor-inducing effect of wounding in initiated NMRI mouse skin. Int. J. Cancer 43, 915–921 (1989).
pubmed: 2714898
doi: 10.1002/ijc.2910430531
Guasch, G. et al. Loss of TGFβ signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell 12, 313–327 (2007). Paper showing how TGFβ signalling promotes cSCC and perturbs tissue homeostasis.
pubmed: 17936557
pmcid: 2424201
doi: 10.1016/j.ccr.2007.08.020
Owens, D. M. & Watt, F. M. Influence of β1 integrins on epidermal squamous cell carcinoma formation in a transgenic mouse model: α3β1, but not α2β1, suppresses malignant conversion1. Cancer Res. 61, 5248–5254 (2001). This paper shows how integrin signalling in cSCC can suppress malignant conversion.
pubmed: 11431366
Owens, D. M. & Watt, F. M. Contribution of stem cells and differentiated cells to epidermal tumours. Nat. Rev. Cancer 3, 444–451 (2003).
pubmed: 12778134
doi: 10.1038/nrc1096
Owens, D. M., Romero, M. R., Gardner, C. & Watt, F. M. Suprabasal α6β4 integrin expression in epidermis results in enhanced tumourigenesis and disruption of TGFβ signalling. J. Cell Sci. 116, 3783–3791 (2003).
pubmed: 12902406
doi: 10.1242/jcs.00725
Quintanilla, M., Brown, K., Ramsden, M. & Balmain, A. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 322, 78–80 (1986).
pubmed: 3014349
doi: 10.1038/322078a0
Wong, C. E. et al. Inflammation and Hras signaling control epithelial-mesenchymal transition during skin tumor progression. Genes Dev. 27, 670–682 (2013).
pubmed: 23512660
pmcid: 3613613
doi: 10.1101/gad.210427.112
Pastushenko, I. et al. Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis. Nature 589, 448–455 (2021).
pubmed: 33328637
doi: 10.1038/s41586-020-03046-1
Dajee, M. et al. NF-κB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature 421, 639–643 (2003).
pubmed: 12571598
doi: 10.1038/nature01283
Ortiz-Urda, S. et al. Type VII collagen is required for Ras-driven human epidermal tumorigenesis. Science 307, 1773–1776 (2005). These findings show how type VII collagen is required for tumour–stroma interactions in cSCC.
pubmed: 15774758
doi: 10.1126/science.1106209
Khavari, P. A. Modelling cancer in human skin tissue. Nat. Rev. Cancer 6, 270–280 (2006).
pubmed: 16541145
doi: 10.1038/nrc1838
Lazarov, M. et al. CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis. Nat. Med. 8, 1105–1114 (2002). This paper reveals the mechanism by which oncogenic Ras controls CDK4 to drive invasive human neoplasia resembling cSCC.
pubmed: 12357246
doi: 10.1038/nm779
Ridky, T. W., Chow, J. M., Wong, D. J. & Khavari, P. A. Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia. Nat. Med. 16, 1450–1455 (2010). This paper establishes an invasive in vitro 3D model of organotypic neoplasia, recapitulating major features of cSCC.
pubmed: 21102459
pmcid: 3586217
doi: 10.1038/nm.2265
Reuter, J. A. et al. Modeling inducible human tissue neoplasia identifies an extracellular matrix interaction network involved in cancer progression. Cancer Cell 15, 477–488 (2009).
pubmed: 19477427
pmcid: 3050547
doi: 10.1016/j.ccr.2009.04.002
Jameson, K. L. et al. IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nat. Med. 19, 626–630 (2013).
pubmed: 23603816
pmcid: 4190012
doi: 10.1038/nm.3165
Goldie, S. J., Chincarini, G. & Darido, C. Targeted therapy against the cell of origin in cutaneous squamous cell carcinoma. Int. J. Mol. Sci. 20, 2201 (2019).
pmcid: 6539622
doi: 10.3390/ijms20092201
Coulombe, P. A., Bernot, K. M. & Lee, C. H. in Encyclopedia of Biological Chemistry 2nd edn (eds Lennarz, W. J. & Lane, M. D.) 665–671 (Academic Press, 2013).
Brown, K., Strathdee, D., Bryson, S., Lambie, W. & Balmain, A. The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted. Curr. Biol. 8, 516–524 (1998).
pubmed: 9560338
doi: 10.1016/S0960-9822(98)70203-9
Bailleul, B. et al. Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter. Cell 62, 697–708 (1990).
pubmed: 1696852
doi: 10.1016/0092-8674(90)90115-U
Greenhalgh, D. A. et al. Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v-Ha-ras oncogene. Mol. Carcinog. 7, 99–110 (1993).
pubmed: 7681293
doi: 10.1002/mc.2940070208
White, A. C. et al. Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proc. Natl Acad. Sci. USA 108, 7425–7430 (2011).
pubmed: 21502519
pmcid: 3088581
doi: 10.1073/pnas.1012670108
Lapouge, G. et al. Identifying the cellular origin of squamous skin tumors. Proc. Natl Acad. Sci. USA 108, 7431–7436 (2011).
pubmed: 21502497
pmcid: 3088632
doi: 10.1073/pnas.1012720108
Lynch, M. D. & Watt, F. M. Fibroblast heterogeneity: implications for human disease. J. Clin. Invest. 128, 26–35 (2018).
pmcid: 5749540
doi: 10.1172/JCI93555
Wong, V. W., Sorkin, M., Glotzbach, J. P., Longaker, M. T. & Gurtner, G. C. Surgical approaches to create murine models of human wound healing. J. Biomed. Biotechnol. 2011, 969618 (2011).
doi: 10.1155/2011/969618
Jonason, A. S. et al. Frequent clones of p53-mutated keratinocytes in normal human skin. Proc. Natl Acad. Sci. 93, 14025–14029 (1996). This study discovers how, in addition to being a tumorigenic mutagen, sunlight acts as a tumour promoter by favouring the clonal expansion of p53-mutant cells in skin.
pmcid: 19488
doi: 10.1073/pnas.93.24.14025
Albibas, A. A. et al. Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin. J. Investig. Dermatol. 138, 189–198 (2018).
doi: 10.1016/j.jid.2017.07.844
Reeves, M. Q., Kandyba, E., Harris, S., Del Rosario, R. & Balmain, A. Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis. Nat. Cell Biol. 20, 699–709 (2018).
pmcid: 6400587
doi: 10.1038/s41556-018-0109-0
Ezhkova, E. et al. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 136, 1122–1135 (2009).
pmcid: 2716120
doi: 10.1016/j.cell.2008.12.043
Hernández-Ruiz, E. et al. The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma. Carcinogenesis 39, 503–513 (2018).
doi: 10.1093/carcin/bgy016
Teknos, T. N. et al. A phase 1 trial of vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma. Invest. N. Drugs 37, 702–710 (2019).
doi: 10.1007/s10637-018-0696-4
Kurundkar, D. et al. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model. Toxicol. Appl. Pharmacol. 266, 233–244 (2013).
doi: 10.1016/j.taap.2012.11.002
Kilgour, J. M. et al. Treatment of cutaneous squamous cell carcinoma with the topical histone deacetylase inhibitor remetinostat. JAMA Dermatol. 158, 105–107 (2022).
doi: 10.1001/jamadermatol.2021.4549
Brown, V. L. et al. p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma. J. Invest. Dermatol. 122, 1284–1292 (2004).
doi: 10.1111/j.0022-202X.2004.22501.x
Hervás-Marín, D. et al. Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma. PLoS ONE 14, e0223341 (2019).
pmcid: 6924689
doi: 10.1371/journal.pone.0223341
Bao, X. et al. CSNK1a1 regulates PRMT1 to maintain the progenitor state in self-renewing somatic tissue. Dev. Cell 43, 227–239 e225 (2017).
pmcid: 5659279
doi: 10.1016/j.devcel.2017.08.021
Sen, G. L., Reuter, J. A., Webster, D. E., Zhu, L. & Khavari, P. A. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature 463, 563–567 (2010).
pmcid: 3050546
doi: 10.1038/nature08683
Darr, O. A. et al. Epigenetic alterations in metastatic cutaneous carcinoma. Head Neck 37, 994–1001 (2015).
doi: 10.1002/hed.23701
Sahai, E. et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 20, 174–186 (2020).
pubmed: 31980749
pmcid: 7046529
doi: 10.1038/s41568-019-0238-1
Hanahan, D. & Coussens, L. M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21, 309–322 (2012).
pubmed: 22439926
doi: 10.1016/j.ccr.2012.02.022
Guo, X. et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat. Med. 24, 978–985 (2018).
pubmed: 29942094
doi: 10.1038/s41591-018-0045-3
Puram, S. V. et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell 171, 1611–1624 e1624 (2017).
pmcid: 5878932
doi: 10.1016/j.cell.2017.10.044
Savas, P. et al. Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis. Nat. Med. 24, 986–993 (2018).
doi: 10.1038/s41591-018-0078-7
Yost, K. E. et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat. Med. 25, 1251–1259 (2019).
pubmed: 31359002
pmcid: 6689255
doi: 10.1038/s41591-019-0522-3
Zheng, C. et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 169, 1342–1356 e1316 (2017).
pubmed: 28622514
doi: 10.1016/j.cell.2017.05.035
Zhang, L. et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature 564, 268–272 (2018).
doi: 10.1038/s41586-018-0694-x
Miao, Y. et al. Adaptive immune resistance emerges from tumor-initiating stem cells. Cell 177, 1172–1186 e1114 (2019).
pmcid: 6525024
doi: 10.1016/j.cell.2019.03.025
Bissell, M. J. & Hines, W. C. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat. Med. 17, 320–329 (2011).
pmcid: 3569482
doi: 10.1038/nm.2328
Flaberg, E. et al. High-throughput live-cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts. Int. J. Cancer 128, 2793–2802 (2011).
doi: 10.1002/ijc.25612
Kalluri, R. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer 16, 582–598 (2016).
doi: 10.1038/nrc.2016.73
Katarkar, A. et al. NOTCH1 gene amplification promotes expansion of cancer associated fibroblast populations in human skin. Nat. Commun. 11, 5126 (2020).
pmcid: 7550609
doi: 10.1038/s41467-020-18919-2
Beebe, E. et al. Defining the molecular landscape of cancer-associated stroma in cutaneous squamous cell carcinoma. J. Invest. Dermatol. 142, 3304–3312 (2022).
pubmed: 35850206
doi: 10.1016/j.jid.2022.06.017
Liu, T. et al. Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy. J. Hematol. Oncol. 12, 86 (2019).
pubmed: 31462327
pmcid: 6714445
doi: 10.1186/s13045-019-0770-1
Khalili, J. S. et al. Oncogenic BRAF(V600E) promotes stromal cell-mediated immunosuppression via induction of interleukin-1 in melanoma. Clin. Cancer Res. 18, 5329–5340 (2012).
pubmed: 22850568
pmcid: 3463754
doi: 10.1158/1078-0432.CCR-12-1632
Nazareth, M. R. et al. Characterization of human lung tumor-associated fibroblasts and their ability to modulate the activation of tumor-associated T cells. J. Immunol. 178, 5552–5562 (2007).
pubmed: 17442937
doi: 10.4049/jimmunol.178.9.5552
Lim, Y. Z. & South, A. P. Tumour-stroma crosstalk in the development of squamous cell carcinoma. Int. J. Biochem. Cell Biol. 53, 450–458 (2014).
pubmed: 24955488
doi: 10.1016/j.biocel.2014.06.012
Berx, G. & van Roy, F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb. Perspect. Biol. 1, a003129 (2009).
pubmed: 20457567
pmcid: 2882122
doi: 10.1101/cshperspect.a003129
Rodriguez, F. J., Lewis-Tuffin, L. J. & Anastasiadis, P. Z. E-cadherin’s dark side: possible role in tumor progression. Biochim. Biophys. Acta 1826, 23–31 (2012).
pubmed: 22440943
pmcid: 3362679
Zhang, Y., Lu, H., Dazin, P. & Kapila, Y. Squamous cell carcinoma cell aggregates escape suspension-induced, p53-mediated anoikis: fibronectin and integrin α
pubmed: 15331608
doi: 10.1074/jbc.M407953200
Schafer, M. & Werner, S. Cancer as an overhealing wound: an old hypothesis revisited. Nat. Rev. Mol. Cell Biol. 9, 628–638 (2008).
pubmed: 18628784
doi: 10.1038/nrm2455
Strieth, S., Hartschuh, W., Pilz, L. & Fusenig, N. E. Angiogenic switch occurs late in squamous cell carcinomas of human skin. Br. J. Cancer 82, 591–600 (2000).
pubmed: 10682671
pmcid: 2363323
doi: 10.1054/bjoc.1999.0969
Azimi, A. et al. Differential proteomic analysis of actinic keratosis, Bowen’s disease and cutaneous squamous cell carcinoma by label-free LC-MS/MS. J. Dermatol. Sci. 91, 69–78 (2018).
pubmed: 29665991
doi: 10.1016/j.jdermsci.2018.04.006
Lichtenberger, B. M. et al. Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 140, 268–279 (2010).
pubmed: 20141840
doi: 10.1016/j.cell.2009.12.046
Beck, B. et al. A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Nature 478, 399–403 (2011).
pubmed: 22012397
doi: 10.1038/nature10525
Argiris, A. et al. Phase III randomized trial of chemotherapy with or without bevacizumab in patients with recurrent or metastatic head and neck cancer. J. Clin. Oncol. 37, 3266–3274 (2019).
pubmed: 31618129
pmcid: 6980834
doi: 10.1200/JCO.19.00555
Mantovani, A., Garlanda, C. & Allavena, P. Molecular pathways and targets in cancer-related inflammation. Ann. Med. 42, 161–170 (2010).
pubmed: 20384432
doi: 10.3109/07853890903405753
Arwert, E. N. et al. Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate. Proc. Natl Acad. Sci. USA 107, 19903–19908 (2010).
pubmed: 21041641
pmcid: 2993377
doi: 10.1073/pnas.1007404107
Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315, 1650–1659 (1986).
pubmed: 3537791
doi: 10.1056/NEJM198612253152606
Naik, S. et al. Inflammatory memory sensitizes skin epithelial stem cells to tissue damage. Nature 550, 475–480 (2017). This paper demonstrates how epidermal stem cells develop a prolonged memory to acute inflammation through altered chromatin accessibility at key response genes, and suggests that this enhanced sensitivity increases susceptibility to cancer.
pubmed: 29045388
pmcid: 5808576
doi: 10.1038/nature24271
Linde, N. et al. Vascular endothelial growth factor-induced skin carcinogenesis depends on recruitment and alternative activation of macrophages. J. Pathol. 227, 17–28 (2012).
pubmed: 22262122
doi: 10.1002/path.3989
Qin, H. et al. Gene therapy for head and neck cancer using vaccinia virus expressing IL-2 in a murine model, with evidence of immune suppression. Mol. Ther. 4, 551–558 (2001).
pubmed: 11735339
doi: 10.1006/mthe.2001.0493
Rohrer, J. W. & Coggin, J. H. Jr CD8 T cell clones inhibit antitumor T cell function by secreting IL-10. J. Immunol. 155, 5719–5727 (1995).
pubmed: 7499859
doi: 10.4049/jimmunol.155.12.5719
Goudie, D. R. et al. Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1. Nat. Genet. 43, 365–369 (2011).
pubmed: 21358634
doi: 10.1038/ng.780
Chen, J. et al. Interferon-γ-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology 217, 385–393 (2012).
pubmed: 22204817
doi: 10.1016/j.imbio.2011.10.016
Strome, S. E. et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res. 63, 6501–6505 (2003).
pubmed: 14559843
Slater, N. A. & Googe, P. B. PD-L1 expression in cutaneous squamous cell carcinoma correlates with risk of metastasis. J. Cutan. Pathol. 43, 663–670 (2016).
pubmed: 27153517
doi: 10.1111/cup.12728
Okiyama, N. & Katz, S. I. Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes. J. Autoimmun. 53, 1–9 (2014).
pubmed: 25047812
pmcid: 4162843
doi: 10.1016/j.jaut.2014.06.005
Arwert, E. N. et al. STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy. Nat. Cell Biol. 22, 758–766 (2020).
pubmed: 32483388
pmcid: 7611090
doi: 10.1038/s41556-020-0527-7
Guy, G. P. Jr, Machlin, S. R., Ekwueme, D. U. & Yabroff, K. R. Prevalence and costs of skin cancer treatment in the US, 2002–2006 and 2007–2011. Am. J. Prev. Med. 48, 183–187 (2015).
pubmed: 25442229
doi: 10.1016/j.amepre.2014.08.036
Singer, D. S. A new phase of the Cancer Moonshot to end cancer as we know it. Nat. Med. 28, 1345–1347 (2022).
pubmed: 35760861
pmcid: 9244436
doi: 10.1038/s41591-022-01881-5
Ernst, A., Grimm, A. & Lim, H. W. Tanning lamps: health effects and reclassification by the Food and Drug Administration. J. Am. Acad. Dermatol. 72, 175–180 (2015).
pubmed: 25458016
doi: 10.1016/j.jaad.2014.10.016
U.S. Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent Skin Cancer (Office of the Surgeon General, 2014).
Force, U. S. P. S. T. et al. Behavioral counseling to prevent skin cancer: US preventive services task force recommendation statement. J. Am. Med. Assoc. 319, 1134–1142 (2018).
doi: 10.1001/jama.2018.1623
Jones, O. T. et al. Artificial intelligence and machine learning algorithms for early detection of skin cancer in community and primary care settings: a systematic review. Lancet Digit. Health 4, e466–e476 (2022).
pubmed: 35623799
doi: 10.1016/S2589-7500(22)00023-1
Force, U. S. P. S. T. et al. Screening for skin cancer: US preventive services task force recommendation statement. J. Am. Med. Assoc. 316, 429–435 (2016).
doi: 10.1001/jama.2016.8465
Riemenschneider, K., Liu, J. & Powers, J. G. Skin cancer in the military: a systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel. J. Am. Acad. Dermatol. 78, 1185–1192 (2018).
pubmed: 29291955
doi: 10.1016/j.jaad.2017.11.062
Weinstock, M. A. et al. Chemoprevention of basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: a randomized clinical trial. JAMA Dermatol. 154, 167–174 (2018).
pubmed: 29299592
pmcid: 5839275
doi: 10.1001/jamadermatol.2017.3631
Chen, A. C. et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N. Engl. J. Med. 373, 1618–1626 (2015).
pubmed: 26488693
doi: 10.1056/NEJMoa1506197
Surjana, D., Halliday, G. M. & Damian, D. L. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis 34, 1144–1149 (2013).
pubmed: 23349012
doi: 10.1093/carcin/bgt017
Carneiro, R. V., Sotto, M. N., Azevedo, L. S., Ianhez, L. E. & Rivitti, E. A. Acitretin and skin cancer in kidney transplanted patients. Clinical and histological evaluation and immunohistochemical analysis of lymphocytes, natural killer cells and Langerhans’ cells in sun exposed and sun protected skin. Clin. Transpl. 19, 115–121 (2005).
doi: 10.1111/j.1399-0012.2004.00311.x
Solomon-Cohen, E., Reiss-Huss, S., Hodak, E. & Davidovici, B. Low-dose acitretin for secondary prevention of keratinocyte carcinomas in solid-organ transplant recipients. Dermatology 238, 161–166 (2022).
pubmed: 33902035
doi: 10.1159/000515496
Patel, G. K. et al. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen’s disease): a randomized, double-blind, placebo-controlled trial. J. Am. Acad. Dermatol. 54, 1025–1032 (2006).
pubmed: 16713457
doi: 10.1016/j.jaad.2006.01.055
Salido-Vallejo, R. et al. Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study. J. Eur. Acad. Dermatol. Venereol. 30, 1120–1124 (2016).
pubmed: 26369617
doi: 10.1111/jdv.13266
Metterle, L., Nelson, C. & Patel, N. Intralesional 5-fluorouracil (FU) as a treatment for nonmelanoma skin cancer (NMSC): a review. J. Am. Acad. Dermatol. 74, 552–557 (2016).
pubmed: 26577512
doi: 10.1016/j.jaad.2015.09.040
Hanlon, A., Kim, J. & Leffell, D. J. Intralesional interferon alfa-2b for refractory, recurrent squamous cell carcinoma of the face. J. Am. Acad. Dermatol. 69, 1070–1072 (2013).
pubmed: 24238178
doi: 10.1016/j.jaad.2013.02.032
Work, G. et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J. Am. Acad. Dermatol. 78, 560–578 (2018).
doi: 10.1016/j.jaad.2017.10.007
Navarrete-Dechent, C., Veness, M. J., Droppelmann, N. & Uribe, P. High-risk cutaneous squamous cell carcinoma and the emerging role of sentinel lymph node biopsy: a literature review. J. Am. Acad. Dermatol. 73, 127–137 (2015).
pubmed: 26089049
doi: 10.1016/j.jaad.2015.03.039
Durham, A. B. et al. Sentinel lymph node biopsy for cutaneous squamous cell carcinoma on the head and neck. JAMA Otolaryngol. Head. Neck Surg. 142, 1171–1176 (2016).
pubmed: 27438434
doi: 10.1001/jamaoto.2016.1927
Maubec, E. et al. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J. Clin. Oncol. 29, 3419–3426 (2011).
pubmed: 21810686
doi: 10.1200/JCO.2010.34.1735
Foote, M. C. et al. Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma. Ann. Oncol. 25, 2047–2052 (2014).
pubmed: 25091317
doi: 10.1093/annonc/mdu368
Migden, M. R. et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 21, 294–305 (2020). Phase II trial showing great promise of PDL1 inhibition in cSCC, changing the field of therapy for advanced cSCC.
pubmed: 31952975
pmcid: 7771329
doi: 10.1016/S1470-2045(19)30728-4
Migden, M. R. et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N. Engl. J. Med. 379, 341–351 (2018).
pubmed: 29863979
doi: 10.1056/NEJMoa1805131
Harwood, C. A., Proby, C. M., Inman, G. J. & Leigh, I. M. The promise of genomics and the development of targeted therapies for cutaneous squamous cell carcinoma. Acta Derm. Venereol. 96, 3–16 (2016).
pubmed: 26084328
doi: 10.2340/00015555-2181
Chang, A. L., Kim, J., Luciano, R., Sullivan-Chang, L. & Colevas, A. D. A case report of unresectable cutaneous squamous cell carcinoma responsive to pembrolizumab, a programmed cell death protein 1 inhibitor. JAMA Dermatol. 152, 106–108 (2016). Seminal paper showing responsiveness to pembrolizumab in unresectable cSCC.
pubmed: 26422398
doi: 10.1001/jamadermatol.2015.2705
Chalmers, Z. R. et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 9, 34 (2017).
pubmed: 28420421
pmcid: 5395719
doi: 10.1186/s13073-017-0424-2
Curiel, C. N. et al. A single arm phase 2 study of talimogene laherparepvec in patients with low-risk invasive cutaneous squamous cell cancer. interim analysis. J. Clin. Oncol. 40, e21583–e21583 (2022).
doi: 10.1200/JCO.2022.40.16_suppl.e21583
Nguyen, T. A., Offner, M., Hamid, O., Zumsteg, Z. S. & Gharavi, N. M. Complete and sustained remission of metastatic cutaneous squamous cell carcinoma in a liver transplant patient treated with talimogene laherparepvec. Dermatol. Surg. 47, 820–822 (2021).
pubmed: 32897942
doi: 10.1097/DSS.0000000000002739
US National Library of Medicine. ClinicalTrials.gov https://ClinicalTrials.gov/show/NCT03714828 (2023).
Rajadhyaksha, M., Marghoob, A., Rossi, A., Halpern, A. C. & Nehal, K. S. Reflectance confocal microscopy of skin in vivo: From bench to bedside. Lasers Surg. Med. 49, 7–19 (2017).
pubmed: 27785781
doi: 10.1002/lsm.22600
Esteva, A. et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature 542, 115–118 (2017).
pubmed: 28117445
pmcid: 8382232
doi: 10.1038/nature21056
Nikolaou, V., Stratigos, A. J. & Tsao, H. Hereditary nonmelanoma skin cancer. Semin. Cutan. Med. Surg. 31, 204–210 (2012).
pubmed: 23174490
pmcid: 3759014
doi: 10.1016/j.sder.2012.08.005
Smith, P. J. & Paterson, M. C. Enhanced radiosensitivity and defective DNA repair in cultured fibroblasts derived from Rothmund Thomson syndrome patients. Mutat. Res. 94, 213–228 (1982).
pubmed: 7099192
doi: 10.1016/0027-5107(82)90183-X
Ghosh, A. K. et al. RECQL4, the protein mutated in Rothmund-Thomson syndrome, functions in telomere maintenance. J. Biol. Chem. 287, 196–209 (2012).
pubmed: 22039056
doi: 10.1074/jbc.M111.295063
Franchitto, A. & Pichierri, P. Protecting genomic integrity during DNA replication: correlation between Werner’s and Bloom’s syndrome gene products and the MRE11 complex. Hum. Mol. Genet. 11, 2447–2453 (2002).
pubmed: 12351580
doi: 10.1093/hmg/11.20.2447
Bolognia, J. L., Schaffer, J. V. & Cerroni, L. Dermatology 4th edn (Elsevier Saunders, 2018).
Emmert, H., Patel, H. & Brunton, V. G. Kindlin-1 protects cells from oxidative damage through activation of ERK signalling. Free Radic. Biol. Med. 108, 896–903 (2017).
pubmed: 28501563
doi: 10.1016/j.freeradbiomed.2017.05.013
Vulliamy, T. J. et al. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood 107, 2680–2685 (2006).
pubmed: 16332973
doi: 10.1182/blood-2005-07-2622
Alter, B. P., Giri, N., Savage, S. A. & Rosenberg, P. S. Cancer in dyskeratosis congenita. Blood 113, 6549–6557 (2009).
pubmed: 19282459
pmcid: 2710915
doi: 10.1182/blood-2008-12-192880
Waterman, E. A. et al. A laminin-collagen complex drives human epidermal carcinogenesis through phosphoinositol-3-kinase activation. Cancer Res. 67, 4264–4270 (2007).
pubmed: 17483338
doi: 10.1158/0008-5472.CAN-06-4141
Tasanen, K., Tunggal, L., Chometon, G., Bruckner-Tuderman, L. & Aumailley, M. Keratinocytes from patients lacking collagen XVII display a migratory phenotype. Am. J. Pathol. 164, 2027–2038 (2004).
pubmed: 15161638
pmcid: 1615787
doi: 10.1016/S0002-9440(10)63762-5
de Jong, S. J. et al. The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to beta-papillomaviruses. J. Exp. Med. 215, 2289–2310 (2018).
pubmed: 30068544
pmcid: 6122964
doi: 10.1084/jem.20170308
Youssefian, L. et al. Epidermodysplasia verruciformis: genetic heterogeneity and EVER1 and EVER2 mutations revealed by genome-wide analysis. J. Invest. Dermatol. 139, 241–244 (2019).
pubmed: 30036492
doi: 10.1016/j.jid.2018.07.010
Rosenberg, P. S., Greene, M. H. & Alter, B. P. Cancer incidence in persons with Fanconi anemia. Blood 101, 822–826 (2003).
pubmed: 12393424
doi: 10.1182/blood-2002-05-1498
Brash, D. E. et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc. Natl Acad. Sci. USA 88, 10124–10128 (1991).
pubmed: 1946433
pmcid: 52880
doi: 10.1073/pnas.88.22.10124
Purdie, K. J. et al. Single nucleotide polymorphism array analysis defines a specific genetic fingerprint for well-differentiated cutaneous SCCs. J. Invest. Dermatol. 129, 1562–1568 (2009).
pubmed: 19131950
pmcid: 3042680
doi: 10.1038/jid.2008.408
Chang, D. & Shain, A. H. The landscape of driver mutations in cutaneous squamous cell carcinoma. NPJ Genom. Med. 6, 61 (2021).
pubmed: 34272401
pmcid: 8285521
doi: 10.1038/s41525-021-00226-4
Pierceall, W. E., Goldberg, L. H., Tainsky, M. A., Mukhopadhyay, T. & Ananthaswamy, H. N. Ras gene mutation and amplification in human nonmelanoma skin cancers. Mol. Carcinog. 4, 196–202 (1991).
pubmed: 2064725
doi: 10.1002/mc.2940040306
Sherr, C. J. & McCormick, F. The RB and p53 pathways in cancer. Cancer Cell 2, 103–112 (2002).
pubmed: 12204530
doi: 10.1016/S1535-6108(02)00102-2
Almquist, L. M. et al. The role of TP53 and MDM2 polymorphisms in TP53 mutagenesis and risk of non-melanoma skin cancer. Carcinogenesis 32, 327–330 (2011).
pubmed: 21123835
doi: 10.1093/carcin/bgq256
William, W. N. Jr et al. Gefitinib for patients with incurable cutaneous squamous cell carcinoma: A single-arm phase II clinical trial. J. Am. Acad. Dermatol. 77, 1110–1113 e1112 (2017).
pubmed: 28964539
pmcid: 5685879
doi: 10.1016/j.jaad.2017.07.048
Jenni, D. et al. A prospective clinical trial to assess lapatinib effects on cutaneous squamous cell carcinoma and actinic keratosis. ESMO Open 1, e000003 (2016).
pubmed: 27843579
pmcid: 5070204
doi: 10.1136/esmoopen-2015-000003
Grob, J. J. et al. Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: a single-arm phase II trial (KEYNOTE-629). J. Clin. 38, 2916–2925 (2020).
doi: 10.1200/JCO.19.03054
Boutros, A. et al. Immunotherapy for the treatment of cutaneous squamous cell carcinoma. Front. Oncol. 11, 733917 (2021).
pubmed: 34513710
pmcid: 8427439
doi: 10.3389/fonc.2021.733917
Maxfield, L., Shah, M., Schwartz, C., Tanner, L. S. & Appel, J. Intralesional 5-fluorouracil for the treatment of squamous cell carcinomas. J. Am. Acad. Dermatol. 84, 1696–1697 (2021).
pubmed: 33378661
doi: 10.1016/j.jaad.2020.12.049
Gualdi, G. et al. Intralesional methotrexate for the treatment of advanced keratinocytic tumors: a multi-center retrospective study. Dermatol. Ther. 10, 769–777 (2020).
doi: 10.1007/s13555-020-00400-z
Lydiatt, W. M. et al. Head and neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J. Clin. 67, 122–137 (2017).
pubmed: 28128848
doi: 10.3322/caac.21389
Jambusaria-Pahlajani, A. et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatol. 149, 402–410 (2013).
pubmed: 23325457
doi: 10.1001/jamadermatol.2013.2456
Ruiz, E. S., Karia, P. S., Besaw, R. & Schmults, C. D. Performance of the American Joint Committee on Cancer Staging Manual, 8th Edition vs the Brigham and Women’s Hospital Tumor Classification System for Cutaneous Squamous Cell Carcinoma. JAMA Dermatol. 155, 819–825 (2019).
pmcid: 6583833
doi: 10.1001/jamadermatol.2019.0032
Wysong, A. et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J. Am. Acad. Dermatol. 84, 361–369 (2021).
doi: 10.1016/j.jaad.2020.04.088
Ibrahim, S. F. et al. Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test. Future Oncol. 18, 833–847 (2022).
doi: 10.2217/fon-2021-1277
Kwiek, B. & Schwartz, R. A. Keratoacanthoma (KA): an update and review. J. Am. Acad. Dermatol. 74, 1220–1233 (2016).
doi: 10.1016/j.jaad.2015.11.033
Goldberg, L. H. et al. Keratoacanthoma as a postoperative complication of skin cancer excision. J. Am. Acad. Dermatol. 50, 753–758 (2004).
pubmed: 15097960
doi: 10.1016/j.jaad.2003.11.065
Schwartz, R. A. Keratoacanthoma: a clinico-pathologic enigma. Dermatol. Surg. 30, 326–333 (2004). discussion 333.
pubmed: 14871228
Ramselaar, C. G., Ruitenberg, E. J. & Kruizinga, W. Regression of induced keratoacanthomas in anagen (hair growth phase) skin grafts in mice. Cancer Res. 40, 1668–1673 (1980).
pubmed: 7370998