a heretofore-unreported mechanism of resistance, specifically high-level amplification of the mutant allele of PIK3CA, which resulted in a marked upregulation of PI3K signaling, enabling resistant cells to regain proliferative capacity at clinically relevant concentrations of the PI3K inhibitor, GDC-0941...
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[16]Hong R, Edgar K, Song K, et al: GDC-0077 is a selective PI3Kalpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies...
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E545K,以及E545区域的其他突变,可能比其他PIK3CA变异体或野生型PIK3CA患者预后较差。也有数据表明E545/542突变可能会对像西妥昔单抗这样的EGFR抑制剂产生耐药性。虽然PIK3CA变种的靶向治疗非常普遍,但仍处于早期临床试验阶段。PIK3CA E545K/E542K are the second most recurrent PIK3CA mutations in breast cancer, and...