Dysregulation of the cyclin dependent kinase pathway in luminal breast cancer creates a new therapeutic opportunity for estrogen receptor positive breast cancer. Initial pan-CDK inhibitors were associated with extensive toxicities but in recent years, the development of potent specific CDK inhibitors with favorable tolerability has driven renewed interests in this class of targeted therapies. Palbociclib, ribociclib and abemaciclib are specific CDK4/6 inhibitors that have been approved by the U.S. Food and Drug Administration for use in combination with endocrine therapy for women with advanced hormone receptor positive breast cancer. These three anticancer therapeutics were approved based on progression free survival benefit seen on phase III trials with the most common grade 3 treatment-related side effects being neutropenia, fatigue, nausea and diarrhea. Except for estrogen receptor positivity, no biomarkers predictive of response to CDK4/6 inhibitors have been identified to date. Based on mechanistic insights here described, CDK4/6 inhibitors are currently being explored in combination with other agents, including targeted therapies, immunotherapy and chemotherapy.

管腔乳腺癌中细胞周期蛋白依赖性激酶途径的失调为雌激素受体阳性乳腺癌创造了新的治疗机会。最初的泛CDK抑制剂与广泛的毒性有关，但是近年来，具有良好耐受性的强效特异性CDK抑制剂的开发引起了人们对这类靶向疗法的新兴趣。Palbociclib，ribociclib和abemaciclib是特定的CDK4 / 6抑制剂，已获得美国食品和药物管理局的批准，可与内分泌疗法联合用于晚期激素受体阳性乳腺癌的妇女。这三种抗癌疗法是根据在III期临床试验中获得的无进展生存获益批准的，该疗法最常见的与3级治疗相关的副作用是中性粒细胞减少，疲劳，恶心和腹泻。迄今为止，除雌激素受体阳性外，尚未鉴定出可预测对CDK4 / 6抑制剂反应的生物标志物。基于此处描述的机理见解，目前正在与其他药物（包括靶向疗法，免疫疗法和化学疗法）联合探索CDK4 / 6抑制剂。