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Published on: July 25, 2020
Biomarkers of therapeutic response to BCL2 antagonists in cancer
Lloyd T Lam1, Haichao Zhang, Brenda Chyla
1Department R4CD, Global Pharmaceutical R&D, Abbott Laboratories, Building AP-10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. lloyd.lam@abbott.com
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.
Insights
Restoring cancer cells
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer cells evade apoptosis, a key mechanism for cell death.
- Dysregulation of apoptosis-regulating proteins contributes to treatment resistance.
- Targeting the intrinsic apoptosis pathway, involving the BCL2 protein family, offers a therapeutic strategy.
Purpose of the Study:
- To review predictive and pharmacodynamic biomarkers for BCL2 antagonists.
- To discuss the importance of companion diagnostics for BCL2 antagonist cancer therapies.
- To explore future directions in biomarker development for apoptosis-targeting agents.
Main Methods:
- Literature review of BCL2 family proteins and their role in apoptosis.
- Analysis of current clinical trials involving BCL2 antagonists.
- Examination of existing and potential biomarker strategies.
Main Results:
- Three BCL2 antagonists are currently in clinical trials.
- Biomarker development is critical for the clinical success of BCL2 antagonists.
- Predictive and pharmacodynamic biomarkers are essential for patient selection and treatment monitoring.
Conclusions:
- Developing companion diagnostics is crucial for BCL2 antagonist efficacy.
- Biomarkers will guide the personalized use of BCL2 antagonists in cancer treatment.
- Further research into novel biomarkers will enhance the therapeutic potential of apoptosis-targeting drugs.
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