Molecular Profiling of Prostate Cancer to Determine Predictive Markers of Response to Radiation and Receptor Tyrosine Kinase Inhibitor Therapy

摘要

Ionizing radiation(IR)induces the activation of PI3K/Akt signaling pathway which in turn regulates endothelial cell viability during treatment with radiotherapy. Inhibition of this pathway by receptor tyrosine kinase inhibitor (TKIs) enhances the cytotoxic effects of radiation in tumor vascular endothelium resulting in improved tumor control. There is significant evidence that multiple receptor tyrosinse kinases may be aberrantly activated in the prostate cancer cells. Therefore we sought to study the effects of broad spectrum small molecule TKIs in the prostate tumor models. We demonstrate that inhibition of this pathway results in improved control of prostate tumor treated with IR via dual effect on both the tumor cells and its microvasculature. Using innovative proteomic technology we plan to identify the molecular profiles that are predictive of response to TKI and IR therapy. Our goal is for these results to provide insights in designing clinical studies aimed at taking these promising pipeline compounds to help treat patients with high risk prostate cancer.