Smith Kathleen J, Haley Heather, Hamza Sate, Skelton Henry G
Quest Diagnostics, Tucker, Georgia 30084, USA.
Dermatol Surg. 2009 Nov;35(11):1766-70. doi: 10.1111/j.1524-4725.2009.01289.x. Epub 2009 Jul 29.
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.
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.
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.
This report is limited because it is a retrospective study that included only patients who developed multiple KA-type SCCs.
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.
蛋白激酶(PKs)对大多数细胞过程不可或缺,PKs失调可导致致癌和抗凋亡途径激活以及免疫失调。
报告接受多激酶抑制剂索拉非尼治疗实体瘤的患者发生角化棘皮瘤(KA)型鳞状细胞癌(SCCs)的情况,阐述这些SCCs诱发的可能机制,并探讨停药及可能的联合治疗以减少此副作用的意义。
15例接受多激酶抑制剂索拉非尼治疗实体瘤的患者发生了多发性KA型SCCs,在患者接受治疗期间这些肿瘤持续发展,但在停用索拉非尼后停止发展。
本报告存在局限性,因为它是一项回顾性研究,仅纳入了发生多发性KA型SCCs的患者。
皮肤SCCs的发生似乎是索拉非尼特有的副作用,索拉非尼是一种多激酶抑制剂,不仅抑制多种酪氨酸激酶(TKs),还抑制丝氨酸 - 苏氨酸激酶Raf。仅抑制TKs的多激酶抑制剂似乎不会使皮肤SCCs的发生率更高。