OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that preclinical data utilizing their pipeline compound OGX-427 was presented at the AACR 102nd Annual Meeting 2011. The study demonstrated the ability of OGX-427 to inhibit Heat Shock Protein 27 (Hsp27), a cell-survival protein believed to play an important role in the proliferation of castrate resistant prostate cancer (CRPC) and resistance to standard therapies.
Hsp27, expressed in prostate cancer and a variety of other malignancies, can be induced by cell stress such as chemotherapy, radiation therapy, and hormone therapy. Molecular chaperones that are heat shock proteins such as Hsp27 act to repair the damage of misfolding of cell structures that can occur when a cell is stressed, thereby enhancing the ability of cancer cells to survive.
The goal of this study was to test the ability of OGX-427, a second-generation antisense therapy, and other mechanisms (siRNA and proteasome inhibition MG132) in silencing the effects of Hsp27. The study showed that OGX-427 inhibits Hsp27 and therefore a cell survival process called autophagy, to increase intracellular unfolded protein burden and cause prostate cancer cell death.
"As cancers become resistant to standard therapies we need to identify new ways to continue to effectively treat them," says Dr. Martin Gleave, Director of The Vancouver Prostate Centre at The University of British Columbia and researcher on this study. "This study confirms the potential utility of inhibiting cell-survival proteins like Hsp27, and the potential for OGX-427 as a novel therapeutic strategy to target for anti-cancer therapies."
These pre-clinical data further support the current OGX-427 development plan in prostate and bladder cancers:
- An Investigator-sponsored Phase 1 clinical trial evaluating OGX-427 administered directly into the bladder in patients with superficial bladder cancer, which was initiated in August 2009.
- An investigator-sponsored, randomized Phase 2 clinical trial evaluating OGX-427 when administered as monotherapy to patients with castrate-resistant prostate cancer. This trial will enroll approximately 72 patients and was initiated in September 2010.
- A planned Phase 2 clinical trial of OGX-427 in approximately 180 patients with metastatic bladder cancer, which is planned to initiate in the second half of 2011.