New Anticancer Zinc Chetatin Agents for Therapy of Advanced Prostate Cancer

(Ref. No. 314-VK)

Background

Castration-resistant prostate cancer is the second leading cause of cancer death among men in the United States. Current treatment options, including chemotherapy, have been shown to improve survival by only 2 to 4 months. Androgen ablation as an advanced prostate cancer therapy dramatically affect the quality of life, including side effects on the cardiovascular system and unclear impact on survival. Thus, development of new therapeutic strategies for advanced prostate cancer is a special need in existing clinical care.

Summary of the Invention

Transformation of normal prostate epithelial cells into cancerous cells involves the loss of ability to accumulate intracellular zinc. This loss of zinc accumulation is one of the most consistent and persistent characteristics of prostatic malignancy. Researchers from Fox Chase Cancer Center have discovered that coupling the delivery of zinc chelating agents with chemo-and/or immunotherapeutic compounds significantly increases the therapeutic index of a given compound and favorable outcome. Newly synthetized chelating agents have been included into a therapeutic strategy that triggers cancer cell death. Zinc sequestration caused the rapid depletion of X-linked inhibitor of apoptosis protein (XIAP), a gatekeeper molecule that determines apoptosis resistance in tumor cells, and significant sensitization of cancer cells to drug-mediated apoptosis. This strategy may exemplify a novel therapeutic regimen with a combined therapy of a zinc chelating and apoptosis-inducing agents. It also provides a powerful tool to test new chelating compounds for drug development.

Makhov P. et al. Zinc chelation induces rapid depletion of the X-linked inhibitor of apoptosis and sensitizes prostate cancer cells to TRAIL-mediated apoptosis. Cell Death Differ. 2008 Nov;15(11):1745-51.