DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Nuclear Tyrosine Kinases: Novel Epigenetic Modulators in Castration-Resistant Prostate Cancer

Principal Investigator: MAHAJAN, NUPAM
Institution Receiving Award: H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, AT SOUTH FLORIDA, UNIVERSITY OF
Program: PCRP
Proposal Number: PC121355
Award Number: W81XWH-14-1-0002
Funding Mechanism: Exploration - Hypothesis Development Award
Partnering Awards:
Award Amount: $126,375.00


PUBLIC ABSTRACT

Prostate cancer patients initially respond to androgen ablation therapy; however, within 18-24 months develop recurrent disease called castration-resistant prostate cancer (CRPC). Therapeutic options for CRPC are very limited. The tyrosine kinases, e.g., Src and Ack1/TNK2, are known to phosphorylate androgen receptor (AR), thus causing CRPC growth. Interestingly, a large majority of the prostate cancers harbor gene fusions. The hypothesis of this project is that tyrosine kinase/AR complex modifies histones at specific sites to facilitate recruitment of enzymes that promote gene fusions. The hypothesis will be tested by performing PCR for gene fusions in prostate cancer cell lines grown in absence of androgen and xenograft tumors grown in castrated nude mice. Deciphering the precise histone phosphorylation marks regulating formation of prostate-specific gene fusions will pave road for designing new therapeutic modalities for CRPC patients.