> Our Work > The Work We Fund

2024 Michael & Lori Milken Family Foundation – PCF Young Investigator Award in Honor of Patrice and Precious Motsepe

Interrogating Underexplored Subtypes of Metastatic Castration Resistant Prostate Cancer

Chien-Kuang Cornelia Ding, MD, PhD
University of California, San Francisco

Mentors: Felix Feng, MD; Eric Small, MD; Michael Haffner, MD, PhD

Description:

  • Metastatic castration resistant prostate cancer (mCRPC) is highly lethal and is well-recognized for its heterogeneity, both across patients and within individual patients and tumors. Several distinct molecular subtypes of mCRPC have been identified, including: 1) classical androgen receptor (AR) expressing adenocarcinoma (AR+/NE-), 2) treatment-emergent neuroendocrine prostate cancer (NEPC) which has lost expression of AR and gained neuroendocrine (NE) features (AR-/NE+), 3) AR+/NE+ “double-positive” amphicrine carcinoma (AMPC), and 4) AR-/NE- “double negative” carcinoma (DNPC). 
  • While diagnostic methods exist for AR+/NE- adenocarcinoma and AR-/NE+ NEPC, the pathologic features and diagnostic criteria for AMPC and DNPC are not established. The presence of these subtypes may alter treatment efficacy and clinical outcomes, making it essential for clinical management to differentiate and diagnose these subtypes. 
  • Dr. Chien-Kuang Cornelia Ding’s project will define clinically relevant pathological diagnostic features among mCRPC and define mCRPC intertumoral heterogeneity. 
  • Tissue specimens from mCRPC cohorts will be examined for pathology-based features that facilitate practical diagnosis and classification of mCRPC subtypes. The clinical significance of these pathological features will be evaluated by their association with overall survival and response to individual therapies. 
  • High-resolution single cell technologies will be used to create a molecular atlas of each mCRPC subtype, to understand how molecular features associate with spatial tissue morphology and indicate intratumoral heterogeneity.
  • If successful, this project will establish diagnostics for mCRPC subtypes and new understandings of the pathological and molecular features of these heterogenous subtypes.  

What this means to patients: mCRPC is highly heterogenous, with multiple molecular subtypes observed both across and within patients. Diagnosis of these subtypes and understanding their molecular features is critical for proper treatment of patients and development of more effective new treatment strategies. Dr. Ding’s project will addresses this fundamental unmet need of pathology diagnosis and classification in mCRPC and enable discovery of diagnostic markers and potentially actionable targets. The results will provide the community with a roadmap to develop new diagnostic and therapeutic strategies specific to each of these subtypes.