The PI3K-AKT-mTOR pathway is frequently activated in cancer. PI3K inhibitors, 
including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-selective 
inhibitor alpelisib (BYL719), currently in clinical development by Novartis 
Oncology, may therefore be effective as anticancer agents. Early clinical 
studies with PI3K inhibitors have demonstrated preliminary antitumor activity 
and acceptable safety profiles. However, a number of unanswered questions 
regarding PI3K inhibition in cancer remain, including: what is the best approach 
for different tumor types, and which biomarkers will accurately identify the 
patient populations most likely to benefit from specific PI3K inhibitors? This 
review summarizes the strategies being employed by Novartis Oncology to help 
maximize the benefits of clinical studies with buparlisib and alpelisib, 
including stratification according to PI3K pathway activation status, selective 
enrollment/target enrichment (where patients with PI3K pathway-activated tumors 
are specifically recruited), nonselective enrollment with mandatory tissue 
collection, and enrollment of patients who have progressed on previous targeted 
agents, such as mTOR inhibitors or endocrine therapy. An overview of 
Novartis-sponsored and Novartis-supported trials that are utilizing these 
approaches in a range of cancer types, including breast cancer, head and neck 
squamous cell carcinoma, non-small cell lung carcinoma, lymphoma, and 
glioblastoma multiforme, is also described.