Emerging Mechanisms of Resistance to Androgen Receptor Inhibitors in Prostate Cancer
By Philip A Watson, V. Arora, C. Sawyers. Nature Reviews. Cancer, 2015
1,370 citations recorded by the source corpus.
During the past 10 years, preclinical studies implicating sustained androgen receptor (AR) signalling as the primary driver of castration-resistant prostate cancer (CRPC) have led to the development of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong the survival of patients with late-stage prostate cancer but are not curative. In this Review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signalling, AR bypass signalling and complete AR independence. This diverse range of resistance mechanisms presents new challenges for long-term disease control, which may be addressable through early use of combination therapies guided by recent insights from genomic landscape studies of CRPC.
Subfields: Cancer Research, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/78ae42de1dfa454da9f7b9da3cd1acd279ce60ee
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In Cancer Research
In Pulmonary and Respiratory Medicine
Citations in the corpus
- Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones (2023, background): “In the clinic, ENZ treatment will ultimately lead to ENZ resistance in patients through several possible mechanisms: (1) activation of AR-bypass signaling, in which other transcription factors (e.g., glucocorticoid receptor [GR]) are induced to substitute AR in order to activate a similar but distin”
- Genetics and biology of prostate cancer (2018, background): “AR bypass in CRPC may also involve the progesterone receptor and themineralocorticoid receptor, which are steroid hormone nuclear receptors structurally related to AR and share substantial homology of the DNA-binding domain with AR (Lu et al. 2006; Watson et al. 2015).”