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Preparation of Peripheral Blood Mononuclear Cell Pellets and Plasma from a Single Blood Draw at Clinical Trial Sites for Biomarker Analysis

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Pharmacodynamic Biomarker Development for PI3K Pathway Therapeutics.

Debra H Josephs¹, Debashis Sarker¹

¹Department of Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London, UK.

Translational Oncogenomics

|February 27, 2016

Summary

This summary is machine-generated.

This review examines pharmacodynamic biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors in cancer clinical trials. It highlights challenges and strategies for integrating these biomarkers for personalized cancer medicine.

Keywords:

PI3K biomarkers therapeutics

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Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

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Area of Science:

Oncology
Molecular Biology
Pharmacology

Background:

The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates critical cellular functions like growth and metabolism.
Aberrant PI3K pathway activation due to mutations is common in various cancers.
Targeted therapies inhibiting the PI3K pathway are under development for cancer treatment.

Purpose of the Study:

To review pharmacodynamic biomarkers used in early-phase clinical trials of PI3K pathway inhibitors.
To discuss challenges in developing and interpreting these biomarkers.
To explore strategies for integrating biomarkers in personalized cancer medicine.

Main Methods:

Literature review of early-phase clinical trials involving PI3K pathway inhibitors.
Analysis of pharmacodynamic biomarker assays and their application.
Discussion of biomarker integration with pharmacokinetic and predictive markers.

Main Results:

Pharmacodynamic biomarkers are crucial for assessing PI3K inhibitor efficacy and target engagement.
Challenges include assay development, validation, and interpretation of results.
Successful integration requires combining pharmacodynamic, pharmacokinetic, and predictive biomarkers.

Conclusions:

Effective pharmacodynamic biomarkers are essential for advancing PI3K pathway inhibitors in oncology.
Overcoming challenges in biomarker development and interpretation is key.
A personalized medicine approach, integrating multiple biomarker types, will optimize PI3K inhibitor therapy for cancer patients.