2017
DOI: 10.1111/bjd.15348
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BRAF inhibitor-associated cutaneous squamous cell carcinoma: new mechanistic insight, emerging evidence for viral involvement and perspectives on clinical management

Abstract: Mutations in the BRAF proto-oncogene occur in the majority of cutaneous melanomas. The commonly detected valine (V) to glutamate (E) mutation (V600E) is known to drive melanomagenesis and has thus been the target of two highly selective chemotherapeutic agents: vemurafenib and dabrafenib. While BRAF inhibitor therapy has revolutionized the treatment of metastatic melanoma, unanticipated cutaneous toxicities, including the development of cutaneous squamous cell carcinomas (cSCCs), are frequently reported and hi… Show more

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Cited by 35 publications
(32 citation statements)
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References 108 publications
(178 reference statements)
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“…Long-term cutaneous inflammation-such as that observed in chronic wounds, burns, scars, ulcers, or sinus tracts-seems to contribute to cSCC development [16]. Pharmacological treatments with BRAF inhibitor monotherapy (i.e., vemurafenib, dabrafenib, or encorafenib) have a higher risk of cSCC development [28] compared to combined BRAF/mitogen-activated protein kinase kinase (MEK) inhibitors [29]. Development of cSCC during vismodegib (a Hedgehog pathway inhibitor) treatment and voriconazole has also been reported [30,31].…”
Section: Risk Factorsmentioning
confidence: 99%
“…Long-term cutaneous inflammation-such as that observed in chronic wounds, burns, scars, ulcers, or sinus tracts-seems to contribute to cSCC development [16]. Pharmacological treatments with BRAF inhibitor monotherapy (i.e., vemurafenib, dabrafenib, or encorafenib) have a higher risk of cSCC development [28] compared to combined BRAF/mitogen-activated protein kinase kinase (MEK) inhibitors [29]. Development of cSCC during vismodegib (a Hedgehog pathway inhibitor) treatment and voriconazole has also been reported [30,31].…”
Section: Risk Factorsmentioning
confidence: 99%
“…However, resistance to BRAFtargeted treatment 4 or immunotherapy 5 reduces the effectiveness of these treatments. Moreover, BRAF inhibitors can cause serious side effects such as squamous cell carcinoma 6 . Therefore, new therapeutic strategies for melanoma are needed.…”
Section: Introductionmentioning
confidence: 99%
“…Evidence of MAPK pathway implications in cSCC pathogenesis derives from studies showing cSCC development in melanoma patients treated with the MAPK inhibitor sorafenib, and with BRAF‐inhibitors as vemurafenib and dabrafenib …”
Section: Molecular Genetics Of Csccmentioning
confidence: 99%