This technology may be used for the treatment of cancers, especially castrate-resistant prostate cancer and other hormonally driven cancers.
Prostate cancer, the most frequently diagnosed non-skin cancer and second leading cancer-related cause of death in men, has long been associated with androgen signaling through the androgen receptor (AR). Although androgen receptor (AR), a member of the nuclear receptor superfamily. Although androgen-depletion therapy is effective, patients commonly develop androgen-independent or castrate-resistant prostate cancer (CRPC) upon treatment, and alternative treatment strategies have been largely unsuccessful. This invention is a combination therapy for CRPC and any other cancer characterized by AR overexpression including AR positive breast cancers. This therapy is also effective on multiple non-hormonal cancers such as pancreatic cancers that appear to rely on signaling by other nuclear receptors.
The combination of Abiraterone, an antiandrogen sold by Johnson & Johnson, with a polo-like kinase 1 (PLK1) inhibitor such as BI2356, substantially reduces cancer cell proliferation and viability of some cancer cells beyond any expectations from an additive model of drug interaction. The use of a Plk1 inhibitor can improve the initial efficacy of Abiraterone, or re-sensitize CRPC cells that have become resistant to Abiraterone. Moreover, the addition of a Plk1 inhibitor can render abiraterone-insensitive cancer cells of disparate origin sensitive to this drug in a manner that correlates with signaling by other nuclear receptors.
Increases initial efficacy of, and can re-sensitizes cancer
cells to, Abiraterone based therapy
- Extend the utility of Abiraterone beyond prostate cancer using gene expression as a stratification biomarker