The Hasan Program Project

Role and rationale in PPG

Leader of Project 1, Cellular Differentiation in Photodynamic Therapy

Project 1 explores this aspect of how the state of cellular growth and differentiation predisposes cells to PDT using ALA-PPIX as the photosensitizer. Specific molecular and cellular basis of the observed effects will be investigated. One is the role of CCAAT-enhancer binding proteins shown to be important regulators of differentiation in skin. A binary approach using a normal physiological model, i.e. keratinocytes of the skin and a neoplastic model, LNCaP prostate tumor cells is proposed. Cellular differentiation will be transiently induced by pharmacological manipulations, such as application of retinoids or vitamin D analogues to skin or to prostate cancer (PCa) implanted in SCID mice and PDT efficacy will be evaluated. The potential significance of these studies is that they may provide a new way to treat cancer. Because the differentiated portions of a tumor (slow-cycling, well-differentiated cells) are often resistant to standard irradiation or chemotherapy, pharmacological manipulation of the differentiation status of the cells may help selectively target these resistant clones. Alternatively, differentiation therapy combined with ALA-based PDT may constitute a new form of adjunctive therapy for less well-differentiated tumors.