Optimization of Photodynamic Therapy Response by Survivin Gene

Abstract

Abstract Cancer is typically a consequence of imbalance between cell death and proliferation in a way favorable to cell proliferation and survival. Most conventional cancer therapies are based on targeting rapidly growing cancerous cells to block growth or enhance cell death, thereby, restoring the balance between these processes. In many instances, malignancies that develop resistance to current treatment modalities, for example photodynamic therapy (PDT), often present the greatest challenge in subsequent management of the patient. In this context, the role of survivin in resistance to anti-cancer therapies has become an area of intensive investigation. Survivin is a member of the inhibitor of apoptosis (IAP) family that correlates inversely with patient prognosis. The application of PDT resulted in an over-expression of survivin in tumor cells and, moreover, survivin has a specific role in modulating PDT-mediated apoptotic response. Tumor cells which present downregulated survivin and then are treated with PDT exhibit increased apoptotic indexes and cytotoxicity when compared to single agent-treated cells. There are several strategies under investigation to target survivin that include of molecular antagonists, small molecules and immunotherapy. The translation of these findings to the clinic is currently ongoing with a number of phase I/II clinical trials targeting survivin that are in progress. Therefore, combining PDT with a survivin inhibitor may attribute to a more favorable clinical outcome than the use of single-modality PDT.