A Novel Targeted Therapy for Treatment-Emergent Anaplastic Forms of Castration-Resistant Prostate Cancer
Abstract
Prostate cancer when confined to the prostate gland, is curable by surgery and/or radiation. However, in advanced prostate cancer where the cancer has spread into the bone and other organs, the emergence of treatment resistance remains inevitable. For decades the primary form of treatment in advanced prostate cancer has been to target the production and actions of male sex hormones and androgens—the primary developmental and survival factor of prostate tissue, which initially results in tumor regression and prolongs cancer control. However, this remission is temporary and treatment resistance occurs, referred to as castrate-resistant prostate cancer. In the past decade, new potent androgen-targeted therapies have been developed and are being introduced earlier into the clinical management of advanced prostate cancer. The sequential and prolonged use of new potent androgen-targeted agents is allowing men to live longer with prostate cancer, but is shifting the natural history of disease toward an increasing emergence of aggressive treatment-resistant forms of castration-resistant prostate cancer. These resistant tumors can have very different characteristics and no longer respond to current androgen-targeted therapies, leaving cytotoxic chemotherapy as the only option. Our team of translational prostate cancer scientists and clinicians, has discovered a protein complex that is overexpressed in a particularly aggressive form of treatment-resistant prostate cancer, known as anaplastic prostate cancer, that is poorly differentiated or taken on characteristics of neuroendocrine prostate cancer. Our team has gathered strong evidence that the inhibition of this protein complex using a new class of drugs, discovered by team members, can slow down the growth and progression of anaplastic prostate cancer. Since there is currently no effective specific therapies for these anaplastic forms of prostate cancer, the studies proposed in our application will test whether this new drug has the potential to be translated from bench-to-bedside and following further development become the first specific targeted therapy for men diagnosed with anaplastic prostate cancer. Importantly, we have found that the protein complex that we are targeting is elevated in metastases that have low prostate-specific membrane antigen levels determined using a minimally invasive clinical imaging procedure. This whole body imaging procedure may give us the ability to improve the selection of patients most likely to respond to our new therapy in future clinical trials. Testing of these strategies in early phase clinical studies will be driven by scientific and clinical team members, and will be overseen by our clinical advisory committee comprising leading international experts in clinical trial design and implementation in the context of advanced prostate cancer. We would anticipate with the expertise of our team members and our established relationship with the pharmaceutical company who has already tested this therapeutic in early phase clinical trials, the outcomes from our study could be translated rapidly into clinical trial testing in metastatic castration-resistant prostate cancer patient cohorts, guided by our research findings in the proposed award. The outcomes of our preclinical translation program has the potential to greatly impact the clinical management of men with treatment-resistant forms of prostate cancer. Not only by providing urgently needed new therapies, but also for improving our ability to match patients with drugs that are effective for their particular disease state. The results from our proposed studies will directly address the FY21 PCRP Overarching Challenges to Define the biology of lethal prostate cancer to reduce death and to Develop treatments that improve outcomes for men with lethal prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210571
Entities
People
- Colleen Nelson
Organizations
- Queensland University of Technology
- United States Army