title: Current treatment of cutaneous squamous cancer and molecular strategies for its sensitization to new target-based drugs.
abstract: BACKGROUND
  Cutaneous squamous cell carcinoma (cSCC) is considered one of the most common skin malignancy with a relatively high risk of metastasis occurrence.
  
  
  METHODS
  We discuss the pathogenetic mechanisms of cSCC and the main therapeutic strategies available for the treatment of cSCC.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Second University of Naples, Department of Biochemistry and Biophysics, Naples Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Nicoletti
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardi
authors.forename: Marina
authors.initials: M
authors.lastname: Di Domenico
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Federica
authors.initials: F
authors.lastname: Zito Marino
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor