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Biomarkers of Therapeutic Response to BCL2 Antagonists in Cancer

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Abstract

Cancer cells persist by resisting programmed cell death or apoptosis. In particular, an imbalance of proteins that regulate apoptosis leads to lack of response to apoptotic stimuli. Thus, restoring the ability of cancer cells to undergo apoptosis is highly desirable. One apoptosis pathway, the intrinsic pathway, involves perturbation of the mitochondria. The major players of this pathway are the members of the B cell CLL/lymphoma 2 (BCL2) family. Currently, three BCL2 antagonists are in clinical trials for cancer treatment. While these antagonists show various specificity and potency, the development of companion diagnostics is crucial for developing these compounds into viable cancer treatments. In this review we describe predictive and pharmacodynamic biomarkers for these agents. Future directions on biomarker development for this class of antagonist are also discussed.

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Acknowledgments

The authors thank the BCL2 project team and tumor genomics team at Abbott Laboratories for their support. They also thank Evelyn McKeegan and Joel Leverson for critically reading the manuscript.

Conflict of interest

All authors are employees of Abbott Laboratories and hold stock or stock options in Abbott Laboratories. They have no other conflicts of interest that are directly relevant to the content of this article.

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  1. Department R4CD, Global Pharmaceutical R&D, Abbott Laboratories, Building AP-10, 100 Abbott Park Road, Abbott Park, IL, 60064, USA

    Lloyd T. Lam, Haichao Zhang & Brenda Chyla

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  1. Lloyd T. Lam
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  2. Haichao Zhang
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  3. Brenda Chyla
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Correspondence to Lloyd T. Lam.

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Lam, L.T., Zhang, H. & Chyla, B. Biomarkers of Therapeutic Response to BCL2 Antagonists in Cancer. Mol Diagn Ther 16, 347–356 (2012). https://doi.org/10.1007/s40291-012-0003-6

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  • DOI: https://doi.org/10.1007/s40291-012-0003-6

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