Prostate cancer accounts for 28% of new cases of cancer and is second in mortality due to cancer in men. Patients who develop only localized tumor have a 5 year-survival rate of almost 100%, however, for patients with metastatic prostate cancer the rate is 31%, and mortality in 90% of cases is the result of systemic dissemination and metastasis. In this project we aim to combine traditional chemotherapy used in the clinic with new viral vectors developed in the Viral Vector Laboratory, São Paulo State Cancer Institute (ICESP) and to evaluate whether the union of different strategies applied to prostate cancer cell lines promotes a synergistic response in the induction of programmed cell death and reduction of tumor progression in an animal model. To this end, we have developed non-replicating adenoviral vectors encoding p53 where expression of this cDNA is controlled by a promoter containing p53-responsive elements, thus establishing a positive feedback mechanism, which should provide greater p53 expression as compared with adenoviral vectors that utilize the constitutive CMV promoter. A second improvement to the adenoviral vector was the modification of the fiber protein with the insertion of the RGD tripeptide, permitting the transduction of target cells, even in the absence of the adenoviral receptor (CAR). Along with these vectors, we plan to apply the chemotherapy drugs Docetaxel, Cabazitaxel and Mitoxantrone with the expectation of increasing cell death. Upon confirmation of the response in vitro and in vivo, one potential perspective of this work would be to extend this study to test prostate cancer cells from patients and evaluate the clinical relevance of this combination therapy.
News published in Agência FAPESP Newsletter about the scholarship: