Abstract:
Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) plays an important role in the development of breast cancer and are closely associated with the resistance to endocrine therapy in advanced breast cancer. Therefore, anti-cancer treatment targeting key molecules in this signaling pathway has become research hot-spot in recent years. Randomized clinical trials have demonstrated that PI3K/AKT/mTOR inhibitors bring significant clinical benefit to patients with advanced breast cancer, especially to those with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer. Alpelisib, a PI3K inhibitor, and everolimus, an mTOR inhibitor, have been approved by Food and Drug Administration. Based on their high efficacy and relatively good safety profile, expanded indication of everolimus in breast cancer have been approved by National Medical Products Administration. Alpelisib is expected to be approved in China in the near future. The members of the consensus expert panel reached this consensus to comprehensively define the role of PI3K/AKT/mTOR signaling pathway in breast cancer, efficacy and clinical applications of PI3K/AKT/mTOR inhibitors, management of adverse reactions, and PIK3CA mutation detection, in order to promote the understanding of PI3K/AKT/mTOR inhibitors for Chinese oncologists, improve clinical decision-making, and prolong the survival of target patient population.
磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路(PAM信号通路)在乳腺癌发生发展中发挥重要作用,与晚期乳腺癌内分泌治疗耐药密切相关,以PAM信号通路中的关键分子为靶点的抗癌治疗成为了近几年的研究热点。靶向PAM信号通路抑制剂为晚期乳腺癌患者尤其是激素受体阳性人表皮生长因子受体2阴性患者带来明显临床获益。目前,美国食品和药物管理局批准上市的PAM信号通路抑制剂包括PI3K抑制剂Alpelisib和mTOR抑制剂依维莫司,同时,依维莫司也在国内获得批准用于乳腺癌新适应证,Alpelisib有望不久在中国上市。鉴于此,专家制定了PAM信号通路抑制剂治疗晚期乳腺癌的临床应用专家共识,系统地介绍了PAM信号通路的机制、PAM信号通路抑制剂的疗效、临床应用、不良事件管理及PIK3CA基因检测建议,旨在提高中国临床肿瘤医师对PAM信号通路抑制剂的认知,推进临床决策的精准性,达到延长患者生存时间的目标。.