Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole genome RNA sequencing, gene set enrichment analysis and immunohistochemistry. Our analyses revealed five mCRPC phenotypes based on the expression of well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: (i) AR-high tumors (ARPC), (ii) AR-low tumors (ARLPC), (iii) amphicrine tumors composed of cells co-expressing AR and NE genes (AMPC), (iv) double-negative tumors (i.e. AR-/NE-; DNPC) and (v) tumors with small…

• UD
  U.S. Department of Defense

  Awards: W81XWH-17-1-0414, PC170431, W81XWH-17, W81XWH-17-1-0415, W81XWH-15-1-0430, W81XWH, W81XWH-15-2-0008, W81XWH-15-1, W81XWH-14-2-0183
• P
  Pfizer
• A
  AstraZeneca
• S
  Sanofi
• GS
  Gilead Sciences
• LF
  Lucas Foundation
• CO
  Clovis Oncology
• B
  BeiGene
• IF
  Institute for Prostate Cancer Research

  Award: P50CA97186
• AP
  Astellas Pharma
• G
  Genentech
• NC
  National Cancer Institute

  Awards: P50CA97186, CA230617, CA163227, P01 CA163227