OncoGenex Pharmaceuticals’ compound OGX-427 shows potential for augmenting anti-cancer therapies and delay tumor progression.
OGX-427 is designed to inhibit Heat Shock Protein 27 (Hsp27), which is expressed in many types of cancers including prostate, bladder, breast and non-small cell lung cancer. Overexpression of Hsp27 is associated with treatment resistance and negative clinical outcomes in patients with various tumor types.
The preclinical study of OGX-427 tested whether the Hsp27 inhibitor worked synergistically with Heat Shock Protein 90 (Hsp90) inhibitors to disrupt protein homeostasis and maximally stress cancer cells to improve treatment outcomes. The study showed when Hsp27 was decreased via OGX-427 treatment, the effect of the Hsp90 inhibitors was enhanced and tumor cell death was observed. The authors concluded OGX-427 in combination with Hsp90 inhibitors potentiated the effects of Hsp90, delayed tumor growth and prolonged survival in murine prostate cancer models.
"As cancers become resistant to standard therapies we need to identify new ways to continue to stress and effectively treat them," said 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 to be included in anti-cancer treatment combination strategies."
OGX-427 is currently being evaluated in several ongoing phase I and II studies in prostate and bladder cancers.