Cell death mechanisms induced by different antitumoral agents (CDM)

Combined therapy:  A new strategy for cancer treatment

Despite extraordinary advances over the last decade, cancer chemotherapy still has two major limitations: the low selectivity of the drugs, leading to serious side effects, and the emergence of resistance, which limits the effectiveness of treatments. Alternative approaches and strategies must be sought that could positively impact on these issues.

Photodynamic therapy is a particular form of chemotherapy in which light is used to activate a photosensitive drug, which confines the therapeutic effect to the illuminated region. The safety of photosensitive drugs in the absence of light, the absence of resistance due to its multitargeted action mechanism, and the absence of severe side effects, enables virtually unlimited repetition of treatments. 

Besides, the combination of drugs is a growing trend in antitumor chemotherapy, to overcome resistance to individual drugs. In this project we propose a development of photodynamic therapy in which conventional drugs are combined with photosensitizing agents to overcome resistance and to improve the effectiveness of the treatments.

First, the effects of drugs and photosensitizing agents supplied individually on the viability of tumor cells in culture, will be evaluated. Subsequently, their toxicity in combination (under the same conditions in which individual toxicity will be evaluated) will be characterized. The most suitable experimental protocol (joint or sequential administration) will be determined to produce the maximum inactivation of cells using the lowest possible concentration of antitumor drug. Morphological studies will also be conducted to characterize cell death mechanisms, changes in the cell morphology and cytoskeletal alterations.