Functional genomic analysis identifies drug targetable pathways in invasive and metastatic cutaneous squamous cell carcinoma.
Aged
Aged, 80 and over
Carcinoma, Squamous Cell
/ genetics
Cell Survival
/ genetics
Disease Progression
Gene Expression
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Genomics
/ methods
Humans
Male
Middle Aged
Mutation
/ genetics
Receptor, EphA6
/ antagonists & inhibitors
Receptor, EphA7
/ antagonists & inhibitors
Signal Transduction
/ genetics
Skin Neoplasms
/ genetics
Small Molecule Libraries
/ pharmacology
Exome Sequencing
/ methods
squamous cell carcinoma of the skin
Journal
Cold Spring Harbor molecular case studies
ISSN: 2373-2873
Titre abrégé: Cold Spring Harb Mol Case Stud
Pays: United States
ID NLM: 101660017
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
15
04
2020
accepted:
09
07
2020
entrez:
27
8
2020
pubmed:
28
8
2020
medline:
7
7
2021
Statut:
epublish
Résumé
Although cutaneous squamous cell carcinoma (cSCC) is treatable in the majority of cases, deadly invasive and metastatic cases do occur. To date there are neither reliable predictive biomarkers of disease progression nor FDA-approved targeted therapies as standard of care. To address these issues, we screened patient-derived primary cultured cells from invasive/metastatic cSCC with 107 small-molecule inhibitors. In-house bioinformatics tools were used to cross-analyze drug responses and DNA mutations in tumors detected by whole-exome sequencing (WES). Aberrations in molecular pathways with evidence of potential drug targets were identified, including the Eph-ephrin and neutrophil degranulation signaling pathways. Using a screening panel of siRNAs, we identified EPHA6 and EPHA7 as targets within the Eph-ephrin pathway responsible for mitigating decreased cell viability. These studies form a plausible foundation for detecting biomarkers of high-risk progressive disease applicable in dermatopathology and for patient-specific therapeutic options for invasive/metastatic cSCC.
Identifiants
pubmed: 32843430
pii: mcs.a005439
doi: 10.1101/mcs.a005439
pmc: PMC7476409
pii:
doi:
Substances chimiques
Small Molecule Libraries
0
Receptor, EphA6
EC 2.7.10.1
Receptor, EphA7
EC 2.7.10.1
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA069533
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA192405
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217862
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224019
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA106195
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA108947
Pays : United States
Informations de copyright
© 2020 Anderson et al.; Published by Cold Spring Harbor Laboratory Press.
Références
Expert Opin Emerg Drugs. 2010 Jun;15(2):185-201
pubmed: 20415599
Science. 2015 May 22;348(6237):880-6
pubmed: 25999502
Clin Chem. 1992 Oct;38(10):2038-43
pubmed: 1394988
Biostatistics. 2004 Oct;5(4):557-72
pubmed: 15475419
Clin Cancer Res. 2014 Dec 15;20(24):6582-92
pubmed: 25303977
Head Neck. 2017 Mar;39(3):578-594
pubmed: 27882625
J Dtsch Dermatol Ges. 2008 Dec;6(12):1066-9
pubmed: 19138272
Clin Cancer Res. 2015 Mar 15;21(6):1447-56
pubmed: 25589618
Methods Mol Biol. 2013;945:161-75
pubmed: 23097107
Nat Commun. 2016 Aug 30;7:12601
pubmed: 27574101
Oncotarget. 2017 Apr 18;8(16):26169-26184
pubmed: 28412732
Mol Oncol. 2016 Oct;10(8):1232-44
pubmed: 27324824
PeerJ. 2019 Jul 10;7:e7313
pubmed: 31333911
Sci Rep. 2016 Sep 26;6:34081
pubmed: 27665737
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
F1000Prime Rep. 2014 Aug 01;6:70
pubmed: 25165569
J Clin Oncol. 2015 Oct 10;33(29):3293-304
pubmed: 26351330
Trends Pharmacol Sci. 2017 Dec;38(12):1085-1099
pubmed: 28964549
Carcinogenesis. 2007 Jun;28(6):1145-52
pubmed: 17234718
JAMA Dermatol. 2017 Mar 1;153(3):296-303
pubmed: 28097368
Cancer Prev Res (Phila). 2010 Jul;3(7):800-9
pubmed: 20570883
J Oncol. 2019 May 23;2019:6273438
pubmed: 31239839
Head Neck. 2011 Dec;33(12):1789-95
pubmed: 22076982
Eur J Cancer. 2015 Sep;51(14):1989-2007
pubmed: 26219687
N Engl J Med. 2001 Mar 29;344(13):975-83
pubmed: 11274625
Oncotarget. 2015 Sep 8;6(26):22587-97
pubmed: 26041887
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8695-700
pubmed: 19433805
Med Sci Monit. 2018 Dec 15;24:9110-9119
pubmed: 30552850
Arch Dermatol. 2007 Jul;143(7):889-92
pubmed: 17638733
J Invest Dermatol. 2017 Aug;137(8):1700-1708
pubmed: 28414022
Cytokine Growth Factor Rev. 2004 Dec;15(6):419-33
pubmed: 15561600
Nucleic Acids Res. 2016 Jan 4;44(D1):D481-7
pubmed: 26656494
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Small GTPases. 2017 Jul 3;8(3):139-163
pubmed: 27442895
Cold Spring Harb Perspect Biol. 2013 Sep 01;5(9):
pubmed: 24003208
Bioinformatics. 2016 Apr 15;32(8):1253-5
pubmed: 26708334
Bioinformatics. 2011 Oct 1;27(19):2648-54
pubmed: 21828086
Cancer Res. 2017 Dec 1;77(23):6614-6626
pubmed: 28951465
Nature. 2018 Oct;562(7728):526-531
pubmed: 30333627
Mol Cancer Res. 2017 Aug;15(8):1106-1116
pubmed: 28461325
Oncogenesis. 2013 Jul 01;2:e54
pubmed: 23817466
Aging (Albany NY). 2019 Aug 22;11(16):6449-6468
pubmed: 31442208
Mol Cancer Ther. 2013 Oct;12(10):1925-34
pubmed: 24072884
J Am Acad Dermatol. 2020 Jun;82(6):1490-1500
pubmed: 31302190
Chin J Cancer. 2015 Sep 14;34(12):614-21
pubmed: 26369827
Cancer Cell. 2016 May 9;29(5):622-637
pubmed: 27165741
Laryngoscope. 2017 Nov;127(11):2565-2569
pubmed: 28581126
Clin Cancer Res. 2020 Jun 15;26(12):3044-3057
pubmed: 32005748
Clin Cancer Res. 2012 Mar 1;18(5):1435-46
pubmed: 22261807
Expert Opin Emerg Drugs. 2010 Sep;15(3):355-73
pubmed: 20557270
Am J Respir Crit Care Med. 2019 Oct 1;200(7):888-899
pubmed: 31166114
J Clin Oncol. 2011 Sep 1;29(25):3419-26
pubmed: 21810686
Clin Cancer Res. 2019 Jul 15;25(14):4211-4223
pubmed: 30814108
Cancer Biol Ther. 2018;19(10):921-933
pubmed: 29856687
PLoS One. 2010 Oct 04;5(10):
pubmed: 20957180
N Engl J Med. 2018 Jul 26;379(4):341-351
pubmed: 29863979
J Am Acad Dermatol. 2013 Jun;68(6):957-66
pubmed: 23375456
Cancer Res. 2013 Jan 1;73(1):285-96
pubmed: 23087056