abiraterone

Overview

Abiraterone acetate is a selective, irreversible inhibitor of CYP17A1 (17α-hydroxylase/C17,20-lyase), blocking androgen biosynthesis in the testes, adrenal glands, and tumor tissue. It is used in combination with prednisone for metastatic castration-resistant and castration-sensitive prostate cancer. In the MSK-CHORD dataset it appears as a recorded systemic therapy for prostate cancer patients.

Evidence in the corpus

  • Abiraterone is listed as a tracked systemic therapy drug in the MSK-CHORD (msk_chord_2024) dataset covering 3,211 PRAD patients. NLP-based annotation of prior treatment history (using transformer models) was used to identify patients who had received abiraterone, enabling post-treatment alteration enrichment analyses including AR and TP53 enrichment after prior systemic therapy in prostate cancer. PMID:39506116
  • Abiraterone pre-treatment context: AR-V7 splice variant was detectable at low ratios in most pre-abiraterone/enzalutamide mCRPC cases; recurrent AR hotspots (T878A, W742C, L702H) that confer agonism predict differential responses to ADT including abiraterone PMID:26000489
  • Variable AR transcriptional output across PRAD subtypes implies subtype-stratified responses to AR-directed therapies; abiraterone named alongside enzalutamide as relevant for SPOP/FOXA1-mutant primary tumors with highest AR output PMID:26544944
  • A patient (WCMC161) whose CRPC-NE liver metastasis arose while on abiraterone therapy provided clonal phylogenetic evidence for divergent evolution from a CRPC-Adeno precursor; CRPC-NE tumors with high NEPC classifier scores are predicted unlikely to respond to further abiraterone or enzalutamide PMID:26855148
  • Only 3 of 63 mCRPC men in the prad_fhcrc rapid-autopsy cohort had received abiraterone; the authors note that the small n prevented assessment of whether this potent AR antagonist induces divergent inter-metastasis resistance mechanisms (AR amplification, AR ligand-binding-domain mutation, AR splice variants). PMID:26928463

Resistance mechanisms

  • AR and TP53 alterations are enriched in PRAD patients with prior systemic therapy (annotated by NLP from clinical notes), consistent with the endocrine-resistance signature seen after androgen deprivation and androgen-receptor–targeted agents including abiraterone. PMID:39506116
  • CRPC-NE, which lacks AR amplification and activating mutations, is the dominant resistance phenotype emerging on abiraterone; the 70-gene NEPC classifier identifies tumors transitioning toward this AR-independent state that are unlikely to benefit from continued abiraterone PMID:26855148

Cancer types (linked)

  • PRAD — metastatic castration-resistant prostate cancer (mCRPC); CRPC-NE subtype emerges as an abiraterone-resistant state PMID:26855148

Sources

This page was processed by entity-page-writer on 2026-05-15.