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Published on: March 6, 2018
The Current Therapeutic Landscape for Metastatic Prostate Cancer
Anastasia Bernal1, Alivia Jane Bechler1, Kabhilan Mohan1
1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68106, USA.
Abstract:
In 2024, there will be an estimated 1,466,718 cases of prostate cancer (PC) diagnosed globally, of which 299,010 cases are estimated to be from the US. The typical clinical approach for PC involves routine screening, diagnosis, and standard lines of treatment. However, not all patients respond to therapy and are subsequently diagnosed with treatment emergent neuroendocrine prostate cancer (NEPC). There are currently no approved treatments for this form of aggressive PC. In this review, a compilation of the clinical trials regimen to treat late-stage NEPC using novel targets and/or a combination approach is presented. The novel targets assessed include DLL3, EZH2, B7-H3, Aurora-kinase-A (AURKA), receptor tyrosine kinases, PD-L1, and PD-1. Among these, the trials administering drugs Alisertib or Cabozantinib, which target AURKA or receptor tyrosine kinases, respectively, appear to have promising results. The least effective trials appear to be ones that target the immune checkpoint pathways PD-1/PD-L1. Many promising clinical trials are currently in progress. Consequently, the landscape of successful treatment regimens for NEPC is extremely limited. These trial results and the literature on the topic emphasize the need for new preventative measures, diagnostics, disease specific biomarkers, and a thorough clinical understanding of NEPC.
Insights
Treatment emergent neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer lacking approved therapies. Promising clinical trials are exploring novel targets like AURKA and receptor tyrosine kinases, but more research is needed.
Area of Science:
- Oncology
- Translational Medicine
- Cancer Research
Background:
- Prostate cancer (PC) affects over 1.4 million globally in 2024, with standard treatments failing some patients.
- Treatment emergent neuroendocrine prostate cancer (NEPC) is an aggressive subtype with no current approved therapies.
- Limited understanding and treatment options highlight an unmet need for NEPC management.
Purpose of the Study:
- To review current clinical trial regimens for treating late-stage NEPC.
- To identify novel therapeutic targets and combination strategies for NEPC.
- To assess the efficacy of emerging treatments for aggressive prostate cancer.
Main Methods:
- Compilation and analysis of ongoing and completed clinical trials for NEPC.
- Assessment of novel targets including DLL3, EZH2, B7-H3, AURKA, receptor tyrosine kinases, PD-L1, and PD-1.
- Evaluation of treatment outcomes for various therapeutic approaches.
Main Results:
- Alisertib (targeting AURKA) and Cabozantinib (targeting receptor tyrosine kinases) show promising results in NEPC treatment.
- Trials targeting PD-1/PD-L1 immune checkpoints demonstrated limited efficacy.
- Several promising clinical trials are underway, indicating active research in NEPC.
Conclusions:
- The landscape for effective NEPC treatment is currently limited, underscoring the need for novel therapeutic strategies.
- Further research into preventative measures, diagnostics, and biomarkers for NEPC is crucial.
- A deeper clinical understanding of NEPC is essential for improving patient outcomes.
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