Background

KAT6A/B are histone acetyl transferases (HATs), a new class of epigenetic regulators. HATs use Ac-CoA as a cofactor and acetylate lysine residues on histones. KAT6 enzymes epigenetically regulate gene expression by acetylating histone proteins.

Dysregulation, including amplifications of Kat6A occurs in multiple cancers including breast, prostate, lung, ovarian and hematological cancers. (1,3)   Kat6A acetylation of key histone residues results in chromatin remodeling and transcriptional activation of genes including the estrogen receptor, cell cycle regulators, and targets of the MYC pathway.  As such, KAT6A is a promising new oncology target particularly in endocrine-resistant breast cancer.

Durable responses with KAT6 inhibition in a Phase 1 study has been reported in ER+ breast cancer, with stable disease reported in some patients with prostate and NSCLC in early studies. (2)  Isosterix has inhibitors that are selective for Kat6A over other HAT family members, including its paralogous protein Kat6B. (4)

References

1. Baell et al, Nature 2018; 560:253-257.

2. Sommerhalder et al, ASCO 2023.

3. Sharma et al, Cell Chemical Biology 2023; 30: 1–20.

4. Rai et. al. PO3-26-04, SABCS Dec 5-9, 2023.