KAT6 inhibitors
First-in-class drugs against the histone acetyltransferases KAT6A and KAT6B, in late trials for hormone receptor-positive breast cancer that has stopped responding to endocrine therapy.
Overview
KAT6A is amplified in a subset of breast cancers and cooperates with the oestrogen receptor to drive gene expression. Inhibitors of KAT6A and KAT6B (PF-07248144, now in phase 3 with fulvestrant, and others) induce senescence in oestrogen receptor-positive breast cancer cells and produced durable responses in heavily pretreated patients in early trials, with dysgeusia and neutropenia as the main side effects. The class is also being explored in prostate cancer and lymphoma.
How it works
Small molecules bind the acetyl-CoA site of KAT6A/B, blocking histone H3 acetylation at oestrogen receptor target genes and triggering senescence.
- New mechanism in endocrine-resistant breast cancer
- Oral
- Combines with fulvestrant and CDK4/6 inhibitors
- Dysgeusia and neutropenia
- No approval yet
Latest papers
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