Understanding KAT6 and Its Role in Breast Cancer
What is KAT6 and why is it important in breast cancer?
KAT6 refers to a protein called lysine acetyltransferase 6 (KAT6A), which is involved in the control of gene activity in cells. KAT6 plays a key role in breast cancers that depend on estrogen [estrogen receptor (ER) positive breast cancers]. Normally, treatments like estrogen blockers and ER degraders try to stop the ER from working, thus slowing or stopping cancer growth. In some cases, however, the ER pathway stays active despite these treatments. This happens because tumor cells learn to use other signals inside the cell to turn on ER-controlled genes without needing estrogen. This ability to "escape" makes tumors resistant. Blocking KAT6 can stop ER activity even when existing drugs don’t work, offering a new way to fight resistant breast cancer.
How do KAT6 inhibitors work in the body against tumors?
KAT6 inhibitors block the activity of KAT6A and a similar protein called KAT6B, stopping them from modifying histones (proteins around which DNA is wrapped). Histone modification normally turns on genes that promote tumor growth so blockage of this activity slows or stops tumor growth.
What have lab and early research studies shown about KAT6 inhibitors?
Laboratory and animal studies have shown that KAT6 inhibitors strongly reduce the growth of breast cancer cells dependent on the estrogen receptor pathway. They have even shown promise against tumors that are resistant to multiple chemotherapy and endocrine therapies.
What have human studies revealed so far?
PF-07248144 was one of the first KAT6A and KAT6B inhibitors studied. In approximately 100 patients who had seen their tumors grow despite existing treatments, PF-07248144, in combination with fulvestrant (a common anticancer treatment for cancers dependent on estrogen) shrank tumors by half or more approximately 30% of the time. This level of response is considered substantial for patients whose tumors are no longer responding to existing hormone treatment. Notable side effects included taste changes and low blood counts.
What other drugs are being studied that target KAT6 or related pathways?
This method of targeting breast cancer is very new and there are very few drugs available at the present time. However, other investigational molecules targeting KAT6 or related proteins include:
· MEN2312: Beginning clinical studies for breast cancer patients who have persistent disease after initial treatment.
· OP-3136: Also beginning clinical studies for breast cancer patients who have persistent disease after initial treatment.
· IDE251: Clinical study in humans planned soon.
Why is this research important for patients and caregivers?
KAT6 inhibitors offer a new approach for patients with ER+/HER2- breast cancer, particularly those who have not responded to current hormone or chemotherapy treatments. Because many patients eventually develop resistance to existing therapies, KAT6 inhibitors provide hope for more effective and less toxic options. Ongoing research is expanding understanding and testing these promising medicines to improve outcomes for breast cancer patients.