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Pharmacodynamic Biomarker Development for PI3K Pathway Therapeutics.

ABSTRACT: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is integral to many essential cell processes, including cell growth, differentiation, proliferation, motility, and metabolism. Somatic mutations and genetic amplifications that result in activation of the pathway are frequently detected in cancer. This has led to the development of rationally designed therapeutics targeting key members of the pathway. Critical to the successful development of these drugs are pharmacodynamic biomarkers that aim to define the degree of target and pathway inhibition. In this review, we discuss the pharmacodynamic biomarkers that have been utilized in early-phase clinical trials of PI3K pathway inhibitors. We focus on the challenges related to development and interpretation of these assays, their optimal integration with pharmacokinetic and predictive biomarkers, and future strategies to ensure successful development of PI3K pathway inhibitors within a personalized medicine paradigm for cancer.

SUBMITTER: Josephs DH

PROVIDER: S-EPMC4762492 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Pharmacodynamic Biomarker Development for PI3K Pathway Therapeutics.

Josephs Debra H DH Sarker Debashis D

Translational oncogenomics 20150101 Suppl 1

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is integral to many essential cell processes, including cell growth, differentiation, proliferation, motility, and metabolism. Somatic mutations and genetic amplifications that result in activation of the pathway are frequently detected in cancer. This has led to the development of rationally designed therapeutics targeting key members of the pathway. Critical to the successful development of these drugs are pharmacodynamic biomarkers th ...[more]

PMID: 26917948

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