Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2023 Mar 9;14:1164514. doi: 10.3389/fimmu.2023.1164514. eCollection 2023.
Breast cancer is one of the common malignancies with poor prognosis worldwide. The treatment of breast cancer patients includes surgery, radiation, hormone therapy, chemotherapy, targeted drug therapy and immunotherapy. In recent years, immunotherapy has potentiated the survival of certain breast cancer patients; however, primary resistance or acquired resistance attenuate the therapeutic outcomes. Histone acetyltransferases induce histone acetylation on lysine residues, which can be reversed by histone deacetylases (HDACs). Dysregulation of HDACs mutation and abnormal expression contributes to tumorigenesis and tumor progression. Numerous HDAC inhibitors have been developed and exhibited the potent anti-tumor activity in a variety of cancers, including breast cancer. HDAC inhibitors ameliorated immunotherapeutic efficacy in cancer patients. In this review, we discuss the anti-tumor activity of HDAC inhibitors in breast cancer, including dacinostat, belinostat, abexinostat, mocetinotat, panobinostat, romidepsin, entinostat, vorinostat, pracinostat, tubastatin A, trichostatin A, and tucidinostat. Moreover, we uncover the mechanisms of HDAC inhibitors in improving immunotherapy in breast cancer. Furthermore, we highlight that HDAC inhibitors might be potent agents to potentiate immunotherapy in breast cancer.
乳腺癌是全球预后较差的常见恶性肿瘤之一。乳腺癌患者的治疗包括手术、放疗、激素治疗、化疗、靶向药物治疗和免疫治疗。近年来,免疫疗法增强了某些乳腺癌患者的生存率;然而,原发性耐药或获得性耐药会降低治疗效果。组蛋白乙酰转移酶在赖氨酸残基上诱导组蛋白乙酰化,组蛋白去乙酰化酶 (HDACs) 可以逆转这种乙酰化。HDAC 的失调突变和异常表达导致肿瘤发生和肿瘤进展。已经开发了许多 HDAC 抑制剂,并在包括乳腺癌在内的多种癌症中显示出强大的抗肿瘤活性。HDAC 抑制剂改善了癌症患者的免疫治疗效果。在这篇综述中,我们讨论了 HDAC 抑制剂在乳腺癌中的抗肿瘤活性,包括达西那妥、贝利司他、阿贝西达、莫塞替尼、帕比司他、罗米地辛、恩替诺特、伏立诺他、普拉克西诺特、他卡西汀、曲古抑菌素 A 和替度司他。此外,我们揭示了 HDAC 抑制剂改善乳腺癌免疫治疗的机制。此外,我们强调 HDAC 抑制剂可能是增强乳腺癌免疫治疗的有效药物。