Molecular pathways in vulvar squamous cell carcinoma: implications for target therapeutic strategies.
Biomarkers, Tumor
Carcinoma, Squamous Cell
/ drug therapy
Cell Cycle
/ genetics
Clinical Decision-Making
Disease Susceptibility
Extracellular Space
/ metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
Intracellular Space
/ metabolism
Molecular Targeted Therapy
Neovascularization, Pathologic
/ genetics
Signal Transduction
Tumor Microenvironment
/ drug effects
Vulvar Neoplasms
/ drug therapy
Disease-free survival
Genes
Molecular pathways
Mutation
Prognosis
Treatment
Vulvar neoplasms
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
01
04
2020
accepted:
17
04
2020
pubmed:
27
4
2020
medline:
17
6
2020
entrez:
27
4
2020
Statut:
ppublish
Résumé
Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed. To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches. We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones. EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability. We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.
Sections du résumé
BACKGROUND
BACKGROUND
Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed.
OBJECTIVES
OBJECTIVE
To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches.
METHODS
METHODS
We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones.
RESULTS
RESULTS
EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability.
CONCLUSIONS
CONCLUSIONS
We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.
Identifiants
pubmed: 32335720
doi: 10.1007/s00432-020-03226-6
pii: 10.1007/s00432-020-03226-6
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Meta-Analysis
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
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