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Last Updated: 10/30/2015

New Assay Detects Drug-induced Cell Death in Tumor Biopsies — A Potential Guide for Treatment Decisions

Measuring anti-cancer drug activity at the tumor site has been difficult because of the inability to optimally detect changes in protein levels (biomarkers) that result from a drug’s actions. This is especially true for drugs that target molecular pathways in cancer cells. Researchers from NCI’s Division of Cancer Treatment and Diagnosis (DCTD) recently developed an assay that measures biomarker levels for a group of anti-cancer drugs that promotes programmed tumor cell death, a molecular process in cells called apoptosis (Srivastava AK, et al., 2015 Clin Cancer Res.). This assay is a first of its kind — while previous measurements of apoptosis proteins could only detect a few or pieces of biomarker proteins, this assay can robustly measure 15 proteins involved in drug-induced apoptosis from a tumor biopsy. The proteins being measured are important in maintaining the balance between pro- and anti- apoptotic factors in a cell, a process that occurs normally when a healthy cell stops growing or even dies if it is damaged badly enough, but becomes imbalanced in cancer. In cancer, proteins that prevent apoptosis are increased, and those that promote it are decreased, which enhances tumor survival. This new assay is groundbreaking because it measures not only this balance of critical proteins that control cell death but also how they interact with one another, providing clearer information to clinicians about the molecular efficacy of the drug. These results may help guide clinical decisions about dosage regimens, resulting in better treatment options and outcomes for the patient. This assay is available as a commercial kit for research use External Link . Information about training courses offered by DCTD on this assay will be available on the DCTD Validated Biomarker Assays website.

Reference:

Srivastava AK, Jaganathan S, Stephen L, Hollingshead MG, Govindharajulu JP, Layhee A, Damour E, Donohue J, Esposito D, Mapes JP, Kinders R, Takebe N, Tomaszewski JE, Kummar S, Doroshow JH, Parchment RE. Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use. Clin Cancer Res. 2016 Feb 15;22(4):1000-10.