Novel Protein Inhibitor CCS1477 Under Study in Treatment-Resistant Prostate Cancer
Posted: Friday, March 12, 2021
Research presented in Cancer Discovery suggests that CCS1477, a novel small-molecule inhibitor of the conserved bromodomain for proteins p300 and CBP, may be a promising therapy for treatment-resistant advanced prostate cancer. Both p300 and CBP help to activate androgen receptor signaling, which in turn fuels cancer growth.
“These initial results are very promising and suggest that the drug could help delay or prevent resistance to the modern hormone treatments abiraterone and enzalutamide, which have already played a critical role in helping patients to live for much longer,” noted Johann S. de Bono, PhD, of the Institute of Cancer Research, in an institutional press release.
Analysis of cell lines and tumor biopsies from 43 patients revealed that CCS1477 activates androgen receptor signaling by binding to proteins p300 and CBP, both cancer gene regulators, and inhibiting their bromodomains. Because bromodomains are responsible for toggling gene activation, their inhibition helps to halt androgen signaling and stymie cancer growth. When p300 and CBP activity in the study samples was blocked, androgen receptor activity declined, and cancer growth slowed. When the proteins’ activity was reactivated, faster growth resumed. These results were repeated when the study samples expanded to include mice with prostate cancer.
Of note, results from this study indicate that CCS1477 could potentially be effective in guarding against genomic changes and adaptations that commonly occur in advanced prostate cancer. The treatment may be effective in resistant disease when combined with hormone therapy. Applications in other types of cancer, including blood, breast, bladder, and lung, may be possible.
“My team and I are already evaluating the new drug in a clinical trial to assess its safety and antitumor activity in men with advanced prostate cancer,” commented Dr. de Bono.
Disclosure: For full disclosures of the study authors, visit cancerdiscovery.aacrjournals.org.