Raimondi Lucrezia, Raimondi Filippo Maria, Pietranera Marta, Di Rocco Arianna, Di Benedetto Laura, Miele Evelina, Lazzeroni Rachele, Cimino Giuseppe, Spinelli Gian Paolo
U.O.C. Territorial Oncology of Aprilia, Sapienza University of Rome, 04011 Aprilia, Italy.
E-Campus University, 00100 Rome, Italy.
Cancers (Basel). 2021 Apr 16;13(8):1928. doi: 10.3390/cancers13081928.
Despite therapeutic improvements, resistance to palbociclib is a growing clinical challenge which is poorly understood. This study was conducted in order to understand the molecular mechanisms of resistance to palbociclib, and to identify biomarkers to predict who will take advantage from cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). A total of about a thousand blood samples were collected from 106 patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who received palbociclib in combination with fulvestrant as the first-line metastatic therapy enrolled in this study. The genotyping of their plasma cell-free DNA was studied, including serial plasma samples. Collectively, our findings identify the appearance of KRAS mutations leading to palbociclib resistance acquisition within 6 months, and provide critical information for the prediction of therapeutic responses in metastatic breast cancer. By monitoring KRAS status through liquid biopsy, we could predict who will take advantage from the combination of palbociclib and fulvestrant, offering highly-individualized treatment plans, thus ensuring the best patient quality of life.
尽管治疗方法有所改进，但对哌柏西利的耐药性仍是一个日益严峻的临床挑战，目前人们对此了解甚少。开展这项研究是为了了解对哌柏西利耐药的分子机制，并确定生物标志物，以预测哪些患者将从细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）中获益。本研究共纳入106例激素受体阳性（HR+）、人表皮生长因子受体2（HER2）阴性的转移性乳腺癌患者，这些患者接受哌柏西利联合氟维司群作为一线转移性治疗，并采集了总共约1000份血样。研究了包括系列血浆样本在内的血浆游离DNA的基因分型。总体而言，我们的研究结果确定了KRAS突变的出现会导致在6个月内获得对哌柏西利的耐药性，并为预测转移性乳腺癌的治疗反应提供了关键信息。通过液体活检监测KRAS状态，我们可以预测哪些患者将从哌柏西利和氟维司群的联合治疗中获益，提供高度个体化的治疗方案，从而确保患者最佳的生活质量。
