Research progress of histone acetyltransferase inhibitors in hormone receptor-positive/HER-2-negative breast cancer

doi:10.3877/cma.j.issn.1674-0807.2026.04.002

Abstract

Abstract:

Hormone receptor-positive and HER-2-negative (HR+/HER-2-) breast cancer is the most common molecular subtype of breast cancer. The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with endocrine therapy regimen has developed as a standard first-line treatment option for patients with HR+/HER-2- advanced breast cancer. In the post-CDK4/6i era, histone acetyltransferases inhibitor (HATi) serves as a new and effective epigenetic therapy. Among them, inhibitors targeting KAT6A inhibits the estrogen signal transduction of HR+/HER-2- breast cancer by regulating the acetylation of tumor cells and its downstream pathway, thereby reversing endocrine resistance. In this article, we summarize the research progress of molecular mechanisms of histone acetyltransferase and HATi in the treatment of HR+/HER-2- breast cancer, and explore its therapeutic prospect in breast cancer treatment.

Key words: Breast neoplasms, Histone acetyltransferase, Hormone receptor, Endocrine therapy

Yujing Tan, Fei Ma. Research progress of histone acetyltransferase inhibitors in hormone receptor-positive/HER-2-negative breast cancer[J]. Chinese Journal of Breast Disease(Electronic Edition), 2026, 20(04): 207-212.

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治疗策略	治疗药物	研究阶段	总例数	既往接受CDK4/6i治疗的人群比例^a	PFS（个月）	P值
CDK4/6i再挑战
MAINTAIN研究^［43］	瑞波西利+内分泌治疗比内分泌治疗单药	2期	119	100%	5.3比2.8	0.006
PACE研究^［44］	哌柏西利+氟维司群比氟维司群	2期	220	100%	4.6比4.8	0.68
postMONARCH研究^［45］	阿贝西利+氟维司群比氟维司群	3期	368	100%	6.0比5.3	0.02
AGAIN研究^［46］	阿贝西利+氟维司群	2期	65	100%	7.1	-
PAM通路抑制剂
EPIK-B5研究^［47］	阿培利司+氟维司群比氟维司群	3期	188 （均携带PIK3CA突变）	100%	7.4比2.8	<0.001
CCTG/BCT MA.40/FINER研究^［40］	Ipatasertib+氟维司群比氟维司群	3期	250	100%	5.3比1.9	<0.001
CAPItello-291研究	Capivertib+氟维司群比氟维司群	3期	708	70.1%（496/708）	7.2比3.6	<0.001
VIKTORIA-1研究^［48］	Gedatolisib+氟维司群+哌柏西利比Gedatolisib+氟维司群比氟维司群	3期	392（均为PIC3CA野生型）	100%	9.3比7.4比2.0	<0.001
NCT06957379^［49］	nab-Sirolimus+氟维司群	2期	65	98.5%（64/65）	PAM通路突变：9.1	-
SERD类药物
EMBER-3研究^［50］	Imlunestrant+阿贝西利比Imlunestrant单药^b	3期	874	100%	ITT： 10.9比5.5； ESR1突变：11.1比5.5	<0.001
evERA研究^［51］	Giredestrant+依维莫司比标准内分泌治疗+依维莫司	3期	373	100%	ITT： 8.8比5.5；ESR1突变：10.0比5.5	<0.001
表观遗传药物
NCT04606446^［31］	KAT6抑制剂PF-07248144+氟维司群	1期	107	100%	≥3线：10.7；2线：未达到	-

治疗策略	治疗药物	研究阶段	总例数	既往接受CDK4/6i治疗的人群比例^a	PFS（个月）	P值
CDK4/6i再挑战
MAINTAIN研究^［43］	瑞波西利+内分泌治疗比内分泌治疗单药	2期	119	100%	5.3比2.8	0.006
PACE研究^［44］	哌柏西利+氟维司群比氟维司群	2期	220	100%	4.6比4.8	0.68
postMONARCH研究^［45］	阿贝西利+氟维司群比氟维司群	3期	368	100%	6.0比5.3	0.02
AGAIN研究^［46］	阿贝西利+氟维司群	2期	65	100%	7.1	-
PAM通路抑制剂
EPIK-B5研究^［47］	阿培利司+氟维司群比氟维司群	3期	188 （均携带PIK3CA突变）	100%	7.4比2.8	<0.001
CCTG/BCT MA.40/FINER研究^［40］	Ipatasertib+氟维司群比氟维司群	3期	250	100%	5.3比1.9	<0.001
CAPItello-291研究	Capivertib+氟维司群比氟维司群	3期	708	70.1%（496/708）	7.2比3.6	<0.001
VIKTORIA-1研究^［48］	Gedatolisib+氟维司群+哌柏西利比Gedatolisib+氟维司群比氟维司群	3期	392（均为PIC3CA野生型）	100%	9.3比7.4比2.0	<0.001
NCT06957379^［49］	nab-Sirolimus+氟维司群	2期	65	98.5%（64/65）	PAM通路突变：9.1	-
SERD类药物
EMBER-3研究^［50］	Imlunestrant+阿贝西利比Imlunestrant单药^b	3期	874	100%	ITT： 10.9比5.5； ESR1突变：11.1比5.5	<0.001
evERA研究^［51］	Giredestrant+依维莫司比标准内分泌治疗+依维莫司	3期	373	100%	ITT： 8.8比5.5；ESR1突变：10.0比5.5	<0.001
表观遗传药物
NCT04606446^［31］	KAT6抑制剂PF-07248144+氟维司群	1期	107	100%	≥3线：10.7；2线：未达到	-

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