Wu Sijia, Xu Junnan, Ma Yiwen, Liang Guilian, Wang Jiaxing, Sun Tao
Breast Medicine Section One, Liaoning Cancer Hospital, Shenyang, Liaoning, China.
Breast Medicine Section One, Liaoning Cancer Hospital, Shenyang, Liaoning 110000, China.
Ther Adv Med Oncol. 2024 Sep 30;16:17588359241282499. doi: 10.1177/17588359241282499. eCollection 2024.
Among women, breast cancer is the most prevalent form of a malignant tumour. Among the subtypes of breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative kinds make up the biggest proportion. The advent of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, which are dependent on cell cycle proteins, has greatly enhanced the prognosis of patients with advanced HR+/HER2- breast cancer. This is a specific treatment that stops the growth of cancer cells by preventing them from dividing. Nevertheless, the drug resistance of the disease unavoidably impacts the effectiveness of treatment and the prognosis of patients. This report provides a thorough analysis of the current research advancements about the resistance mechanism of CDK4/6 inhibitors in HR+/HER2- breast cancer. It presents an in-depth discussion from numerous viewpoints, such as aberrant cell cycle regulation and changes in signalling pathways. In response to the drug resistance problem, subsequent treatment strategies are also being explored, including switching to other CDK4/6 inhibitor drugs, a combination of novel endocrine therapeutic agents, an optimal combination of targeted therapies and switching to chemotherapy. An in-depth study of the resistance mechanism can assist in identifying creative tactics that can overcome or postpone drug resistance, alleviate the problem of restricted treatment strategies following drug resistance and enhance the prognosis of patients.
在女性中，乳腺癌是恶性肿瘤最常见的形式。在乳腺癌的亚型中，激素受体（HR）阳性和人表皮生长因子受体（HER2）阴性类型占比最大。依赖细胞周期蛋白的细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂的出现，极大地改善了晚期HR+/HER2-乳腺癌患者的预后。这是一种通过阻止癌细胞分裂来抑制其生长的特异性治疗方法。然而，该疾病的耐药性不可避免地影响治疗效果和患者预后。本报告全面分析了目前关于HR+/HER2-乳腺癌中CDK4/6抑制剂耐药机制的研究进展。它从多个角度进行了深入讨论，如异常的细胞周期调控和信号通路变化。针对耐药问题，后续也在探索治疗策略，包括换用其他CDK4/6抑制剂药物、联合新型内分泌治疗药物、靶向治疗的优化组合以及改用化疗。深入研究耐药机制有助于找到能够克服或延缓耐药性的创新策略，缓解耐药后治疗策略受限的问题，并改善患者预后。
