Introduction: Cutaneous squamous cell carcinoma (cSCC) is considered one of the most common skin malignancy with a relatively high risk of metastasis occurrence.
Areas covered: We discuss the pathogenetic mechanisms of cSCC and the main therapeutic strategies available for the treatment of cSCC.
Expert opinion: 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.