In the present Marie Curie Intra European Fellowship application, HYPERTAM, we propose to combine our recent complementary findings in two separate anticancer therapeutic modalities, namely, photodynamic therapy of cancer (PDT) with hypericin or other phototoxins and tamoxifen chemotherapy, fusing them in one combinatorial treatment predicted to demonstrate enhanced antitumoural potency through synergy of tamoxifen action with hypericin photo-inactivation (inhibition) of mitochondrial complex III quinoloxidizing centre. The main points to be addressed by HYPERTAM are summarized as follows: (i) Revisit and expound the tamoxifen - complex III inhibitor cytotoxic interplay findings. (ii) Explore the predicted hypericin PDT-tamoxifen synergistic action in selected cell models. (iii) Evaluate other photosensitizers with high clinical relevance. (iv) Investigate the cell death pathways implicated in the most striking in-vitro results (v) translate the most important in-vitro combinatorial treatment results to corresponding animal models for a pilot preclinical assessment.
The fellowship is expected give the applicant a unique opportunity to acquire key skills and knowledge like: (i) competences in molecular biology including evaluation of cell death mechanisms and pathways (ii) competencies in the use of novel lab techniques and instrumentation (iii) certified competencies in animal tumour models. (iv) competencies in management, administration and entrepreneurial activities. The possibility to run HYPERTAM represents a unique opportunity for the applicant to perfect his professional profile, and at a very critical juncture, steer his career towards independent research. The expected result of the proposed project, a cross-disciplinary bimodal anticancer treatment modality with high potency, is of high socioeconomic value, and is expected to greatly contribute to European excellence and competitiveness.
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