Clinical Advances in Hematology & OncologyBiomarkers and Novel PET Imaging to Detect Neuroendocrine Prostate Cancer

Exploring the Detection and Dynamics of Neuroendocrine Prostate Cancer: Insights into Lineage Plasticity and Novel Diagnostic Tools

In an in-depth exploration of neuroendocrine prostate cancer (NEPC), Dr. Rahul Aggarwal sheds light on the aggressive nature of NEPC, distinguishing between its de novo and treatment-emergent forms. His insights delve into the underpinnings of these cancer types, their detection challenges, and the promising horizon of diagnostic and therapeutic strategies. This summary encapsulates the key takeaways from Dr. Aggarwal’s discussion, highlighting the significance of advanced biomarkers, novel PET imaging techniques, and the evolving landscape of NEPC treatment.

Key Points:

• NEPC is an aggressive subtype of prostate cancer, with de novo cases being rare (<1%) and treatment-emergent forms occurring in up to 15-20% of metastatic castration-resistant prostate cancer cases.
• The genesis of de novo NEPC is not fully understood but is associated with the deletion or inactivation of tumor suppressor genes, notably RB1 and TP53.
• Treatment-emergent NEPC emerges as an escape mechanism from androgen deprivation therapy (ADT), facilitated by lineage plasticity—a process of epigenetic modification leading to cancer cell transformation.
• Lineage plasticity, potentially reversible in preclinical models, raises hope for therapeutic interventions that could revert NEPC back to adenocarcinoma.
• Detection of NEPC poses challenges, especially for the treatment-emergent form, which requires biopsy of metastatic sites. Morphological and pathological features significantly differ between de novo NEPC and typical prostate adenocarcinoma.
• Novel PET imaging techniques and biomarkers, including liquid biopsy, are under investigation to improve noninvasive detection of NEPC, with trials exploring tracers like delta-like ligand 3 (DLL3).
• PET imaging offers the potential to visualize tumor heterogeneity and the varying levels of neuroendocrine differentiation across different lesions.
• Treatment strategies for NEPC diverge from conventional prostate cancer therapies, with de novo NEPC being unresponsive to hormone therapy and treated similarly to small cell cancers.
• Ongoing research includes the development of zirconium 89 PET imaging agents targeting CD46, and methylation profiling of circulating tumor DNA, showcasing the promise of innovative diagnostic tools.
• Investigational approaches for NEPC treatment focus on immunotherapeutics, novel chemoimmunotherapy combinations, and targeting epigenetic dysregulation.

“We do not yet know whether it is possible clinically, but it has been shown to be possible in preclinical models.”
– Dr. Rahul Aggarwal, on the reversibility of lineage plasticity in prostate cancer

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