The DF/HCC Prostate Cancer SPORE, initially funded in 2002 and led by Philip Kantoff, MD (DFCI), has been highly successful in creating cohesion in the Prostate Cancer Program, sparking new RO1, PO1, and DOD grants, fostering innovative ideas in prostate cancer research, and advancing the careers of junior investigators. The renewal application, submitted in September 2006, features new projects as well as extensions of existing ones.
- The first project, led by Mark Rubin, MD (BWH), Todd Golub, MD (DFCI/Broad), and Kantoff, features a unique approach to distinguishing aggressive from indolent forms of prostate cancer. Investigators will analyze gene expression differences among paraffin-embedded specimens from a large cohort of untreated patients, who have been followed until death and who have, for the most part, not died of prostate cancer.
- The second project, led by Matthew Freedman, MD (DFCI/Broad), and Oliver Sartor, MD (DFCI), aims to better understand the role of the newly discovered 8q24 genetic-risk allele on prostate cancer biology and to determine the effects of this genetic variant on both clinical presentation and outcomes.
- The third project, led by William Hahn, MD, PhD, (DFCI/Broad) and Glenn Bubley, MD (BIDMC), proposes to develop synergistic combination therapies that include targeting two pathways: AR and mTOR. This project will require combining whole-genome genetic analyses on human tumors with state-of-the-art imaging techniques, clinical investigation, and comprehensive genetic tools to identify kinase inhibitors effective in prostate cancer.
- The fourth project, led by Golub and William Oh, MD (DFCI), will take new approaches to targeting two critical transcription factors in the evolution of prostate cancer: AR and the ETS family. This project will determine whether inhibition of HSP90 -- and the consequent inhibition of AR activity -- is associated with clinical response; it will also identify and test the activity of small molecules that inhibit TMPRSS2/ERG activity.
- The fifth project, led by Steve Balk, MD, PhD, (BIDMC) and Myles Brown, MD (DFCI), will build on progress made (1) validating the important role of AR in androgen-independent prostate cancer (AICaP) by testing the effectiveness of blocking the production of AR ligands and inhibiting Cdk1, a kinase that stabilizes and activates AR; and (2) integrating the gene expression dataset from AICaP bone marrow metastases with gene expression and ChIP-on-chip data from AICaP cell lines and xenografts, to back-translate from the clinic to the laboratory and identify potential new therapeutic targets. Ultimately, investigators will vet the new targets that become candidates for future iterations of clinical translation.