Department of Breast and Thyroid Surgery, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Breast and Thyroid Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510623, P.R. China.
Int J Mol Med. 2022 Oct;50(4). doi: 10.3892/ijmm.2022.5184. Epub 2022 Aug 31.
In recent years, the incidence rate of breast cancer has increased year by year, and it has become a major threat to the health of women globally. Among all breast cancer subtypes, the hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) luminal subtype breast cancer is the most common form of breast cancer. Cyclin‑dependent kinase 4 and 6 (CDK4/6) inhibitors, the hotspots in the field of targeted therapy for breast cancer, have proved to exhibit a good effect on patients with HR/HER2 breast cancer in a number of clinical trials, but the problem of drug resistance is inevitable. At present, three specific CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have been approved by the USA Food and Drug Administration for the first‑line treatment of HR/HER2 breast cancer. The drug resistance mechanisms of CDK4/6 inhibitors can be divided into cell cycle‑specific resistance and cell cycle non‑specific resistance. With the discovery of the drug resistance mechanism of CDK4/6 inhibitors, various targeted strategies have been proposed. The present review mainly discusses the mechanism of CDK4/6 inhibitors, drug resistance mechanisms and treatment strategies after resistance.
近年来，乳腺癌的发病率逐年上升，已成为全球女性健康的重大威胁。在所有乳腺癌亚型中，激素受体（HR）/人表皮生长因子受体 2（HER2）阳性的腔面型乳腺癌是最常见的乳腺癌类型。细胞周期蛋白依赖性激酶 4 和 6（CDK4/6）抑制剂是乳腺癌靶向治疗领域的热点，在多项临床试验中已被证明对 HR/HER2 阳性乳腺癌患者具有良好的疗效，但耐药问题不可避免。目前，三种特异性 CDK4/6 抑制剂（帕博西尼、瑞博西林和阿贝西利）已被美国食品药品监督管理局批准用于 HR/HER2 阳性乳腺癌的一线治疗。CDK4/6 抑制剂的耐药机制可分为细胞周期特异性耐药和细胞周期非特异性耐药。随着对 CDK4/6 抑制剂耐药机制的发现，提出了各种靶向策略。本文主要讨论 CDK4/6 抑制剂的作用机制、耐药机制以及耐药后的治疗策略。
