在HER-2阴性乳腺癌中导航PI3K/AKT通路的复杂性:生物标志物及其他方面
M Sirico1, F Jacobs2, C Molinelli3
1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Critical reviews in oncology/hematology
|May 30, 2024
概括
新的PI3K/AKT抑制剂对转移性乳腺癌具有特定基因变异的治疗有希望. 像PIK3CA突变这样的生物标志物是关键的,但最佳的患者选择和抵抗机制需要进一步研究.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 遗传学 遗传学 是一个
背景情况:
- 激素受体阳性 (HR+) /人体表皮生长因子受体2 (HER2) 阴性转移性乳腺癌 (mBC) 治疗已通过向疗法取得进展.
- 氨酸3-酶通路抑制剂 (PI3Ki),如阿尔佩利西布,和AKT抑制剂 (AKTi),如卡皮瓦塞蒂布,为患有PIK3CA/AKT1/PTEN变异的患者提供好处.
- 这些向疗法具有显著的毒性,限制了对脆弱患者群体的使用.
研究的目的:
- 审查HR+/HER-mBC中对PI3K/AKT抑制剂 (PI3K/AKTis) 的反应和耐药性的生物标志物.
- 为了确定患者群体最有可能从PI3K / AKTis在早期和晚期疾病环境中受益.
- 评估PI3K/AKT途径向剂的开发,成功和失败情况.
主要方法:
- 分析来自SOLAR-1和CAPItello-291等试验的临床数据.
- 对生物标志物的审查,包括PIK3CA,AKT,PTEN突变,胰岛素水平和18F-FDG-PET/CT.
- 对药物开发管道和临床结果的评估.
主要成果:
- PIK3CA突变和AKT通路改变显示出对alpelisib和capivasertib疗效的潜在预测价值.
- 来自回顾性和探索性分析的数据并不具有决定性.
- 检测PIK3CA/AKT1/PTEN变化的最佳诊断方法尚未建立.
结论:
- PI3K/AKT抑制剂为特定的mBC亚型提供治疗选择,但毒性和耐药性仍然是挑战.
- 准确的生物标志物识别对于患者选择和最大化治疗效益至关重要.
- 在疾病进展过程中重新评估PIK3CA突变状态对于个性化治疗策略至关重要.
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