Phosphatidylinositide-3-kinase inhibitors: addressing questions of isoform selectivity and pharmacodynamic/predictive biomarkers in early clinical trials.

摘要

In Journal of Clinical Oncology, Bendell et al1 present a clinical phase I dose-escalation study of the orally bioavailable phosphatidylinositide-3-kinase (PI3K) inhibitor NVP-BKM120. Over the last 2 years, preliminary conference reports have described the initial phase I clinical experience for several PI3K inhibitors with different selectivity profiles.2 The article from Bendell et al is the first full peer-reviewed publication reporting the phase I clinical results with a pan-class I selective PI3K inhibitor lacking activity against mammalian target of rapamycin (mTOR).3 Briefly, the authors report that NVP-BKM120 is well tolerated with an acceptable dose-dependent safety profile.