Biomarkers of response and resistance to PI3K inhibitors in estrogen receptor-positive breast cancer patients and combination therapies involving PI3K inhibitors

被引:61
作者
Brandao, M. [1 ]
Caparica, R. [1 ]
Eiger, D. [1 ]
de Azambuja, E. [1 ,2 ]
机构
[1] Inst Jules Bordet, Acad Trials Promoting Team, Brussels, Belgium
[2] Inst Jules Bordet, Med Oncol Dept, Brussels, Belgium
关键词
breast neoplasms; predictive biomarkers; PI3K inhibitors; PIK3CA; gene sequencing; BUPARLISIB PLUS TRASTUZUMAB; PHASE-II TRIAL; PIK3CA MUTATIONS; DOUBLE-BLIND; EVEROLIMUS EFFICACY; PATHWAY; IB; SENSITIVITY; PICTILISIB; PACLITAXEL;
D O I
10.1093/annonc/mdz280
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In this review, we discuss biomarkers of response and resistance to PI3K inhibitors (PI3Ki) in estrogen receptor-positive breast cancer, both in the early and advanced settings. We analyse data regarding PIK3CA mutations, PI3K pathway activation, PTEN expression loss, Akt signalling, insulin levels, (18F)FDG-PET/CT imaging, FGFR1/2 amplification, KRAS and TP53 mutations. Most of the discussed data comprise retrospective and exploratory studies, hence many results are not conclusive. Therefore, among all of these biomarkers, only PIK3CA mutations have proved to have a predictive value for treatment with the alpha-selective PI3Ki alpelisib (SOLAR-1 trial) and the beta-sparing PI3Ki taselisib (SANDPIPER trial) in the advanced setting. Since the accuracy of current individual biomarkers is not optimal, a composite biomarker, including DNA, RNA and protein expression data, to more precisely assess the PI3K/AKT/mTOR pathway activation status, may arise as a promising approach. Finally, we describe the rational for new combination therapies involving PI3Ki and anti-HER2 agents, chemotherapy, CDK4/6 inhibitors, mTOR inhibitors or new endocrine treatments and discuss the ongoing trials in this field.
引用
收藏
页码:27 / 42
页数:16
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