An F876L Mutation in Androgen Receptor Confers Genetic and Phenotypic Resistance to MDV3100 (Enzalutamide)
Harvard University · Dana-Farber Cancer Institute
Abstract
UNLABELLED: Castration-resistant prostate cancer (CRPC) is the most aggressive, incurable form of prostate cancer. MDV3100 (enzalutamide), an antagonist of the androgen receptor (AR), was approved for clinical use in men with metastatic CRPC. Although this compound showed clinical efficacy, many initial responders later developed resistance. To uncover relevant resistant mechanisms, we developed a model of spontaneous resistance to MDV3100 in LNCaP prostate cancer cells. Detailed characterization revealed that emergence of an F876L mutation in AR correlated with blunted AR response to MDV3100 and sustained proliferation during treatment. Functional studies confirmed that AR(F876L) confers an…
Citation impact
- FWCI
- 47.33
- Percentile
- 100%
- References
- 33
Authors
16- MKManav KorpalCorresponding
Harvard University, Dana-Farber Cancer Institute
- JMJoshua M. Korn
Harvard University, Dana-Farber Cancer Institute
- XGXueliang Gao
Harvard University, Dana-Farber Cancer Institute
- DPDaniel P. Rakiec
Harvard University, Dana-Farber Cancer Institute
- DADavid A. Ruddy
Harvard University, Dana-Farber Cancer Institute
Topics & keywords
- Enzalutamide
- Prostate cancer
- Androgen receptor
- Medicine
- LNCaP
- Cancer research
- Pharmacology
- Phenotype
- Good health and well-being