Targeting Apoptosis in Cancer
Puneet Singh1, Bora Lim2,3
1Division of Surgery, Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Psingh6@mdanderson.org.
Purpose Of Review:
Apoptosis is a major mechanism of cancer cell death. Thus, evasion of apoptosis results in therapy resistance. Here, we review apoptosis modulators in cancer and their recent developments, including MDM2 inhibitors and kinase inhibitors that can induce effective apoptosis.
Recent Findings:
Both extrinsic pathways (external stimuli through cell surface death receptor) and intrinsic pathways (mitochondrial-mediated regulation upon genotoxic stress) regulate the complex process of apoptosis through orchestration of various proteins such as members of the BCL-2 family. Dysregulation within these complex steps can result in evasion of apoptosis. However, via the combined evolution of medicinal chemistry and molecular biology, omics assays have led to innovative inducers of apoptosis and inhibitors of anti-apoptotic regulators. Many of these agents are now being tested in cancer patients in early-phase trials. We believe that despite a sluggish speed of development, apoptosis targeting holds promise as a relevant strategy in cancer therapeutics.
Insights
Cancer cells evade apoptosis, leading to therapy resistance. New apoptosis modulators, like MDM2 and kinase inhibitors, show promise in overcoming this resistance and offer a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis is a critical mechanism for cancer cell death.
- Evasion of apoptosis contributes to therapeutic resistance in cancer.
- Understanding apoptosis pathways is key to developing novel cancer treatments.
Purpose of the Study:
- To review recent developments in apoptosis modulators for cancer therapy.
- To highlight novel agents targeting apoptosis pathways.
- To assess the therapeutic potential of apoptosis-targeting strategies.
Main Methods:
- Review of current literature on apoptosis modulators in cancer.
- Analysis of recent advancements in medicinal chemistry and molecular biology.
- Examination of clinical trial data for apoptosis-targeting agents.
Main Results:
- Dysregulation of both extrinsic and intrinsic apoptosis pathways contributes to cancer.
- MDM2 inhibitors and kinase inhibitors are emerging as effective apoptosis inducers.
- Several novel apoptosis-targeting agents are currently in early-phase clinical trials.
Conclusions:
- Targeting apoptosis remains a promising strategy in cancer therapeutics.
- Despite development challenges, apoptosis modulators offer potential for overcoming therapy resistance.
- Continued research in medicinal chemistry and molecular biology is crucial for advancing apoptosis-based cancer treatments.
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