根据世界卫生组织国际癌症研究机构数据显示，2020 年全球总计新增 1930 万癌症病例，女性乳腺癌已超过肺癌，成为最常见的癌症，新增病例达 230 万。其中激素受体阳性(HR+)乳腺癌占据了主要比例，传统治疗方式为内分泌治疗(ET)，然而 ET 治疗产生耐药性是不可避免的。直至 2015 年全球首个选择性 CDK4/6抑制剂哌柏西利获得批准上市，CDK4/6 抑制剂与 ET 的联合作用才得以克服对 ET 的耐药性，显著改善患者的生存时间和生活质量，使得晚期 HR+ 乳腺癌的治疗发生了革命性变化。然而，由于固有性和获得性耐药的存在，仍有部分患者对 CDK4/6 抑制剂治疗无反应或治疗后不久产生耐药。受限于对药物耐药机制的了解有限，无法预测患者用药的疗效及耐药性。因此，迫切需要可靠的预测性生物标志物来指导患者用药的选择和新型药物组合的研发。本文就目前有关 CDK4/6 抑制剂的预测性生物标志物的最新进展进行综述。
According to data from the International Agency for Research on Cancer of the World Health Organization,there were a total of 19.3 million new cancer cases worldwide in 2020,with breast cancer surpassing lung cancer as the most common cancer,accounting for 2.3 million new cases.Among them,hormone receptor-positive(HR+)breast cancer occupies a major proportion,and the traditional treatment approach is endocrine therapy(ET).However,the development of resistance to ET is inevitable.It wasn't until 2015 when the world's first selective CDK4/6 inhibitor,palbociclib,was approved and introduced to the market that the combination of CDK4/6 inhibitors and ET overcomes resistance to ET and significantly improves the patients'survival time and quality of life,which has revolutionized the therapy of advanced HR+ breast cancer.Despite this breakthrough,some patients still do not respond to CDK4/6 inhibitor treatment or develop resistance shortly after initiation due to the presence of innate and acquired resistance.It is a challenge to predict treatment efficacy and resistance in patients for the limited understanding of mechanisms.Therefore,there is an urgent need for reliable predictive biomarkers to guide treatment selection for patients and facilitate the development of novel drug combinations.This article provides a comprehensive review of the latest advances in predictive biomarkers for CDK4/6 inhibitors.
breast cancerCDK4/6 inhibitorbiomarkerendocrine therapyresistance
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