apalutamide

Overview

Apalutamide (ARN-509) is a second-generation nonsteroidal androgen receptor (AR) antagonist that competitively inhibits androgen binding and blocks AR nuclear translocation and transcriptional activity. It is used in the treatment of prostate adenocarcinoma (PRAD), including non-metastatic castration-resistant prostate cancer. The AR F877L point mutation has been identified as an acquired resistance mechanism to apalutamide.

Evidence in the corpus

• AR F877L resistance mutation detected via MSK-IMPACT in an mCRPC patient progressing after 4 years on apalutamide (ARN-509); the same mutation also confers resistance to enzalutamide, demonstrating cross-resistance between second-generation AR antagonists PMID:28825054.

Resistance mechanisms

• AR F877L — gain-of-function point mutation in the ligand-binding domain; confers resistance to both apalutamide and enzalutamide; detected clonally by targeted sequencing in a patient with clinical progression after 4 years of apalutamide therapy PMID:28825054.

Cancer types (linked)

• PRAD — prostate adenocarcinoma; castration-resistant and non-metastatic castration-resistant disease settings PMID:28825054.

Sources

• PMID:28825054 — Abida et al. 2017, MSK-IMPACT pan-prostate cancer genomic profiling (504 tumors, 451 patients); describes AR F877L resistance to apalutamide.

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