Second University of Naples, Department of Biochemistry and Biophysics, Naples Italy.
Expert Opin Biol Ther. 2013 Jan;13(1):51-66. doi: 10.1517/14712598.2012.725720. Epub 2012 Sep 24.
Cutaneous squamous cell carcinoma (cSCC) is considered one of the most common skin malignancy with a relatively high risk of metastasis occurrence.
We discuss the pathogenetic mechanisms of cSCC and the main therapeutic strategies available for the treatment of cSCC.
Chemotherapy and biological therapy with Interferon α (IFN-α) and cis retinoic acid are active but give limited results. Recently, strategies based on the use of molecularly target-based agents (MTA) have been used with promising results. Based on the available findings, we hypothesize that SCC cells can develop survival and resistance mechanisms to MTAs. The detection of these mechanisms could be useful in designing strategies able to overcome the latter and to potentiate the anticancer activity of MTAs. We describe the example of the EGF-dependent survival pathway elicited by IFN-α and the different strategies to abrogate this survival pathway. Other strategies to potentiate the antitumor activity of cytotoxic agents such as docetaxel or cisplatin are also discussed. Illuminating examples are the inhibition of multichaperone activity or the inactivation of the proteasome. In conclusion, a new dawn based upon the rationale use of MTAs is rising up in the treatment of advanced cSCC.
皮肤鳞状细胞癌(cSCC)被认为是最常见的皮肤恶性肿瘤之一,其转移发生的风险相对较高。
我们讨论了 cSCC 的发病机制和治疗 cSCC 的主要治疗策略。
化疗和生物疗法,如干扰素 α(IFN-α)和维甲酸,具有活性,但效果有限。最近,基于使用分子靶向药物(MTA)的策略已取得了有希望的结果。根据现有研究结果,我们假设 SCC 细胞可能会产生对 MTA 的生存和耐药机制。检测这些机制可能有助于设计能够克服这些机制并增强 MTA 抗癌活性的策略。我们描述了由 IFN-α引发的 EGF 依赖性生存途径的例子,以及阻断该生存途径的不同策略。还讨论了增强细胞毒性药物(如多西紫杉醇或顺铂)抗肿瘤活性的其他策略。抑制多功能伴侣活性或蛋白酶体失活就是很好的例子。总之,基于合理使用 MTA 的新策略正在为治疗晚期 cSCC 带来新的曙光。