Migliaccio Ilenia, Leo Angela, Galardi Francesca, Guarducci Cristina, Fusco Giulio Maria, Benelli Matteo, Di Leo Angelo, Biganzoli Laura, Malorni Luca
"Sandro Pitigliani" Translational Research Unit, Hospital of Prato, Azienda USL Toscana Centro, 59100 Prato, Italy.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Cancers (Basel). 2021 May 27;13(11):2640. doi: 10.3390/cancers13112640.
CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are the standard treatment for patients with hormone receptor-positive and HER2 negative (HR+/HER2-) metastatic breast cancer. Patients might show intrinsic and acquired resistance, which leads to treatment failure and progression. Circulating biomarkers have the potential advantages of recognizing patients who might not respond to treatment, monitoring treatment effects and identifying markers of acquired resistance during tumor progression with a simple withdrawal of peripheral blood. Genomic alterations on circulating tumor DNA and serum thymidine kinase activity, but also circulating tumor cells, epigenetic or exosome markers are currently being tested as markers of CDK4/6i treatment response, even though none of these have been integrated into clinical practice. In this review, we discuss the recent advancements in the development of circulating biomarkers of CDK4/6i response in patients with HR+/HER2-breast cancer.
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）和内分泌治疗是激素受体阳性且人表皮生长因子受体2阴性（HR+/HER2-）转移性乳腺癌患者的标准治疗方法。患者可能会出现原发性和获得性耐药，从而导致治疗失败和疾病进展。循环生物标志物具有潜在优势，即通过简单采集外周血，就能识别可能对治疗无反应的患者、监测治疗效果以及在肿瘤进展过程中识别获得性耐药的标志物。目前正在测试循环肿瘤DNA上的基因组改变、血清胸苷激酶活性，以及循环肿瘤细胞、表观遗传或外泌体标志物，以作为CDK4/6i治疗反应的标志物，尽管这些均未纳入临床实践。在本综述中，我们讨论了HR+/HER2-乳腺癌患者中CDK4/6i反应循环生物标志物开发方面的最新进展。
