Southwest Prostate Cancer Symposium Archives

Novel Targeted Treatments for Metastatic Disease

Posted by Alan H. Bryce, MD | Nov 2023

Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, discusses the limitations of traditional treatments for metastatic prostate cancer, such as androgen deprivation therapy (ADT) and chemotherapy, which, while effective initially, often lead to resistance and progression. He emphasizes the need for innovative approaches that target specific molecular pathways involved in prostate cancer growth and metastasis.
He highlights several promising targeted therapies currently under investigation. One is the use of PARP inhibitors, such as olaparib and rucaparib, which target cancer cells with defective DNA repair mechanisms, particularly those with BRCA1/2 mutations. Dr. Bryce also discusses the role of androgen receptor (AR) pathway inhibitors, including novel agents like enzalutamide and enzalutamide, which provide more potent and selective inhibition of AR signaling than traditional ADT.
Dr. Bryce switches focuses to radiopharmaceuticals, such as lutetium-177 (Lu-177) PSMA-617, which deliver targeted radiation to prostate-specific membrane antigen (PSMA)-expressing cells. Clinical trials indicate that this approach can effectively reduce tumor burden and improve clinical outcomes in patients with advanced prostate cancer. Additionally, he explores the potential of immunotherapies, including immune checkpoint inhibitors and vaccines, in treating metastatic prostate cancer.

Identifying Mutations and Optimizing Use of PARP Inhibitors

Posted by William K. Oh, MD | Nov 2023

William K. Oh, MD, highlights the growing significance of precision medicine and the role of genetic profiling in tailoring therapeutic strategies. Dr. Oh begins by outlining the importance of identifying DNA repair gene mutations, particularly BRCA1 and BRCA2, in prostate cancer patients. These mutations, which impair the cell’s ability to repair DNA damage, render the cancer more susceptible to treatments targeting DNA repair mechanisms, such as PARP inhibitors.

Dr. Oh delves into the mechanisms of PARP inhibitors, which function by inhibiting the poly (ADP-ribose) polymerase (PARP) enzyme involved in DNA repair. By blocking this pathway, PARP inhibitors induce synthetic lethality in cancer cells harboring defective DNA repair genes, leading to cell death.

Dr. Oh discusses the importance of patient selection based on genetic profiling and the potential for combining PARP inhibitors with other therapies, such as androgen receptor signaling inhibitors and immune checkpoint inhibitors, to enhance their efficacy. He reviews ongoing clinical trials exploring these combination strategies and their preliminary results.

Cardiovascular Side Effects of Advanced Disease Therapies

Posted by William K. Oh, MD | Nov 2023

William K. Oh, MD, details the common therapies used in advanced prostate cancer, including androgen deprivation therapy (ADT), novel hormonal agents like abiraterone and enzalutamide, and chemotherapies such as docetaxel. He emphasizes that while these treatments are effective in controlling cancer progression and improving survival, they have significant cardiovascular risks.
The lecture presents evidence from multiple studies demonstrating that ADT is associated with an increased risk of cardiovascular events, including myocardial infarction, stroke, and sudden cardiac death. Dr. Oh discusses the underlying mechanisms, such as metabolic changes, increased insulin resistance, and adverse lipid profiles induced by hormone deprivation.
Dr. Oh emphasizes the importance of a multidisciplinary approach in managing patients undergoing these treatments. He advocates for regular cardiovascular monitoring, risk assessment, and the involvement of cardiologists in the care team to mitigate these risks.

Immunotherapy in Metastatic Prostate Cancer

Posted by A. Oliver Sartor, MD | Nov 2023

A. Oliver Sartor, MD, highlights immunotherapy and its goal of harnessing and enhancing the body’s immune system to target and eradicate cancer cells. He emphasizes the distinct mechanisms of immunotherapeutic agents compared to traditional treatments, noting their potential to offer durable responses and improved survival outcomes in specific patient populations.
Dr. Sartor reviews sipuleucel-T, the first FDA-approved immunotherapy for metastatic castrate-resistant prostate cancer (mCRPC), and its ability to extend overall survival, despite minimal impact on disease progression markers like PSA levels. He also addresses the role of immune checkpoint inhibitors, such as pembrolizumab, particularly for mCRPC patients with specific biomarkers like microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). He presents data from recent studies showing promising responses in these subsets of patients, highlighting the importance of genetic profiling in identifying candidates for checkpoint inhibition.
Additionally, Dr. Sartor explores emerging immunotherapeutic approaches, including the use of chimeric antigen receptor (CAR) T-cell therapy and novel vaccines targeting prostate-specific antigens. He discusses the ongoing clinical trials evaluating these innovative treatments and their potential to transform the therapeutic landscape of metastatic prostate cancer.

Metastatic Castrate-Resistant Prostate Cancer: Options and Possible Sequences

Posted by A. Oliver Sartor, MD | Nov 2023

Dr. A. Oliver Sartor outlines the available therapeutic options for metastatic castrate-resistant prostate cancer (mCRPC), which include novel hormonal agents, chemotherapy, immunotherapy, and targeted therapies. He addresses androgen receptor signaling inhibitors such as abiraterone acetate and enzalutamide, and the use of chemotherapy agents like docetaxel and cabazitaxel.

Dr. Sartor also addresses the emerging role of immunotherapy in mCRPC, particularly with agents like pembrolizumab for patients with specific genetic mutations or microsatellite instability. Additionally, he discusses the potential of radionuclide therapies, such as radium-223.