Destroy the truncated androgen receptor that hormone drugs cannot touch
In advanced prostate cancer, a shortened form of the hormone receptor loses the very part existing drugs bind to. A drug that destroys the whole protein would still work.
AR-V7 lacks the ligand-binding domain, so enzalutamide and abiraterone cannot act on it, and its presence predicts resistance. Degraders and N-terminal-domain binders that engage full-length AR and its splice variants could restore control. Full-length AR degraders have reached the clinic; variant-competent agents are the unmet need, and AR-V7 status is already measurable in circulating tumour cells.
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
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not linked directly; found by shared links- IdeaAn open degrader consortium against every undruggable driver transcription factor
Shares Arvinas, PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.
- ProductBicalutamide
Shares Androgen receptor signalling, Androgen receptor, Prostate cancer.
- ProductApalutamide
Shares Androgen receptor signalling, Androgen receptor, Prostate cancer.
- Key paperThe first PROTAC: a chimeric molecule that tags a protein for destruction
Shares Androgen receptor, PROTACs & molecular glues (targeted protein degradation), The undruggable drivers, Acquired resistance to every therapy.
- ProductDarolutamide
Shares Androgen receptor signalling, Androgen receptor, Prostate cancer.
- PersonShaomeng Wang
Shares Androgen receptor, PROTACs & molecular glues (targeted protein degradation).
- TermAR-V7 splice variant
Shares Androgen receptor signalling, Androgen receptor, Prostate cancer.
- IdeaDegrade the damaged p53 protein rather than trying to repair it
Shares PROTACs & molecular glues (targeted protein degradation), The undruggable drivers.