Chen Jing, Wan Runlan, Li Qinqin, Rao Zhenghuan, Wang Yanlin, Zhang Lei, Teichmann Alexander Tobias
Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People's Republic of China.
Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Cancer Cell Int. 2021 Jun 10;21(1):306. doi: 10.1186/s12935-021-01999-5.
Drug resistance is always a great obstacle in any endocrine therapy of breast cancer. Although the combination of endocrine therapy and targeted therapy has been shown to significantly improve prognosis, refractory endocrine resistance is still common. Dysregulation of the Hippo pathway is often related to the occurrence and the development of many tumors. Targeted therapies of this pathway have played important roles in the study of triple negative breast cancer (TNBC). Targeting the Hippo pathway in combination with chemotherapy or other targeted therapies has been shown to significantly improve specific antitumor effects and reduce cancer antidrug resistance. Further exploration has shown that the Hippo pathway is closely related to endocrine resistance, and it plays a "co-correlation point" role in numerous pathways involving endocrine resistance, including related pathways in breast cancer stem cells (BCSCs). Agents and miRNAs targeting the components of the Hippo pathway are expected to significantly enhance the sensitivity of breast cancer cells to endocrine therapy. This review initially explains the possible mechanism of the Hippo pathway in combating endocrine resistance, and it concludes by recommending endocrine therapy in combination with therapies targeting the Hippo pathway in the study of endocrine-resistant breast cancers.
耐药性始终是乳腺癌任何内分泌治疗中的巨大障碍。尽管内分泌治疗与靶向治疗联合应用已显示可显著改善预后，但难治性内分泌耐药仍很常见。Hippo通路失调常与多种肿瘤的发生发展相关。该通路的靶向治疗在三阴性乳腺癌（TNBC）研究中发挥了重要作用。已表明靶向Hippo通路联合化疗或其他靶向治疗可显著提高特定抗肿瘤效果并降低癌症耐药性。进一步探索表明，Hippo通路与内分泌耐药密切相关，且在涉及内分泌耐药的众多通路中起“共关联点”作用，包括乳腺癌干细胞（BCSC）中的相关通路。靶向Hippo通路成分的药物和miRNA有望显著增强乳腺癌细胞对内分泌治疗的敏感性。本综述首先解释了Hippo通路对抗内分泌耐药的可能机制，并在文末建议在内分泌耐药乳腺癌研究中，将内分泌治疗与靶向Hippo通路的治疗联合应用。
