BACKGROUND: Protein kinases (PKs) are indispensable for most cellular processes, and deregulation of PKs can lead to activation of oncogenic and anti-apoptotic pathways and immune dysregulation. OBJECTIVE: To report the development of keratoacanthoma (KA)-type squamous cell carcinomas (SCCs) in patients treated with the multikinase inhibitor sorafenib for the treatment of solid tumors, to present the possible mechanisms for induction of these SCCs, and to discuss the implications for discontinuation of therapy and possible cotherapies to decrease this side effect. PARTICIPANTS: Fifteen patients taking the multikinase inhibitor sorafenib for the treatment of solid tumors who developed multiple KA-type SCCs, which continued to develop while the patients were undergoing therapy but stopped with discontinuation of sorafenib. LIMITATIONS: This report is limited because it is a retrospective study that included only patients who developed multiple KA-type SCCs. CONCLUSIONS: Development of cutaneous SCCs appears to be a side effect limited to sorafenib, a multikinase inhibitor that inhibits not only multiple tyrosine kinases (TKs), but also the serine-threonine kinase Raf. The incidence of cutaneous SCCs does not appear greater with multikinase inhibitors that inhibit only TKs.
BACKGROUND: Protein kinases (PKs) are indispensable for most cellular processes, and deregulation of PKs can lead to activation of oncogenic and anti-apoptotic pathways and immune dysregulation. OBJECTIVE: To report the development of keratoacanthoma (KA)-type squamous cell carcinomas (SCCs) in patients treated with the multikinase inhibitor sorafenib for the treatment of solid tumors, to present the possible mechanisms for induction of these SCCs, and to discuss the implications for discontinuation of therapy and possible cotherapies to decrease this side effect. PARTICIPANTS: Fifteen patients taking the multikinase inhibitor sorafenib for the treatment of solid tumors who developed multiple KA-type SCCs, which continued to develop while the patients were undergoing therapy but stopped with discontinuation of sorafenib. LIMITATIONS: This report is limited because it is a retrospective study that included only patients who developed multiple KA-type SCCs. CONCLUSIONS: Development of cutaneous SCCs appears to be a side effect limited to sorafenib, a multikinase inhibitor that inhibits not only multiple tyrosine kinases (TKs), but also the serine-threonine kinase Raf. The incidence of cutaneous SCCs does not appear greater with multikinase inhibitors that inhibit only TKs.
Authors: Emily Y Chu; Karolyn A Wanat; Christopher J Miller; Ravi K Amaravadi; Leslie A Fecher; Marcia S Brose; Suzanne McGettigan; Lydia R Giles; Lynn M Schuchter; John T Seykora; Misha Rosenbach Journal: J Am Acad Dermatol Date: 2012-05-18 Impact factor: 11.527
Authors: Tatiana C Schneider; Ellen Kapiteijn; Tom van Wezel; Jan W A Smit; Jacobus J M van der Hoeven; Hans Morreau Journal: BMC Cancer Date: 2016-01-19 Impact factor: 4.430