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中华乳腺病杂志(电子版) ›› 2026, Vol. 20 ›› Issue (04) : 207 -212. doi: 10.3877/cma.j.issn.1674-0807.2026.04.002

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组蛋白乙酰转移酶抑制剂在激素受体阳性/HER-2阴性乳腺癌中的研究进展
谭玉靓, 马飞()   
  1. 100021 北京,国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院肿瘤内科
  • 收稿日期:2026-01-12 出版日期:2026-08-01
  • 通信作者: 马飞
  • 基金资助:
    国家科技重大专项(2023ZD0502200)

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

Yujing Tan, Fei Ma()   

  1. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
  • Received:2026-01-12 Published:2026-08-01
  • Corresponding author: Fei Ma
引用本文:

谭玉靓, 马飞. 组蛋白乙酰转移酶抑制剂在激素受体阳性/HER-2阴性乳腺癌中的研究进展[J/OL]. 中华乳腺病杂志(电子版), 2026, 20(04): 207-212.

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

激素受体阳性/HER-2阴性(HR+/HER-2-)乳腺癌是占比最高的乳腺癌亚型,其晚期患者的一线标准治疗为细胞周期蛋白依赖性激酶4/6抑制剂(CDK4/6i)联合内分泌治疗。在后CDK4/6i时代,应用组蛋白乙酰转移酶抑制剂(HATi)是一类全新、有效的表观遗传治疗策略。其中,靶向KAT6A分子的抑制剂通过调节肿瘤细胞的乙酰化及其下游通路,抑制HR+/HER-2-乳腺癌的雌激素信号转导,从而逆转内分泌耐药。本文总结了组蛋白乙酰转移酶在乳腺癌发生发展中的分子机制、HATi治疗HR+/HER-2-乳腺癌的研究进展,探索HATi在HR+/HER-2-乳腺癌中的应用策略和治疗前景。

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.

图1 KAT6作用机制示意图 注:Ac 为乙酰基;K 为赖氨酸;KAT 为赖氨酸乙酰转移酶;BRPF为含溴结构域与 PHD 锌指蛋白 ;MEAF6 为 MYST/Esa1 相关因子 6;ING5 为生长抑制因子 5;H3 为组蛋白 H3;p53 为肿瘤蛋白 p53;ER为雌激素受体
表1 HR+/HER-2-晚期乳腺癌患者CDK4/6i治疗进展后不同治疗方案的生存结局
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
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
NCT0695737949 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
NCT0460644631 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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