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Updated: Feb 15, 2026
Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
Published on: August 21, 2013
Negative regulators of cell death pathways in cancer: perspective on biomarkers and targeted therapies
Ali Razaghi1, Kirsten Heimann2, Patrick M Schaeffer2
1Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville, QLD, 4811, Australia. ali.razaghi@my.jcu.edu.au.
Abstract:
Cancer is a primary cause of human fatality and conventional cancer therapies, e.g., chemotherapy, are often associated with adverse side-effects, tumor drug-resistance, and recurrence. Molecularly targeted therapy, composed of small-molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer vaccines), is a less harmful alternative being more effective against cancer cells whilst preserving healthy tissues. Drug-resistance, however, caused by negative regulation of cell death signaling pathways, is still a challenge. Circumvention of negative regulators of cell death pathways or development of predictive and response biomarkers is, therefore, quintessential. This review critically discusses the current state of knowledge on targeting negative regulators of cell death signaling pathways including apoptosis, ferroptosis, necroptosis, autophagy, and anoikis and evaluates the recent advances in clinical and preclinical research on biomarkers of negative regulators. It aims to provide a comprehensive platform for designing efficacious polytherapies including novel agents for restoring cell death signaling pathways or targeting alternative resistance pathways to improve the chances for antitumor responses. Overall, it is concluded that nonapoptotic cell death pathways are a potential research arena for drug discovery, development of novel biomarkers and targeted therapies.
Insights
Targeting cancer cell death pathways, including apoptosis and non-apoptotic routes, offers a promising strategy to overcome drug resistance. Research into biomarkers for these pathways is crucial for developing effective cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Conventional cancer therapies like chemotherapy often lead to drug resistance and recurrence.
- Molecularly targeted therapies offer a less toxic alternative but face challenges with drug resistance.
- Negative regulation of cell death signaling pathways contributes significantly to cancer drug resistance.
Purpose of the Study:
- To review the current knowledge on targeting negative regulators of cell death signaling pathways.
- To evaluate advances in biomarkers for negative regulators of cell death.
- To provide a platform for designing effective polytherapies against cancer.
Main Methods:
- Critical discussion of existing literature on targeting apoptosis, ferroptosis, necroptosis, autophagy, and anoikis.
- Evaluation of clinical and preclinical research on biomarkers associated with negative regulators.
- Synthesis of information to guide future therapeutic strategies.
Main Results:
- Negative regulators of cell death pathways are key contributors to cancer drug resistance.
- Biomarkers for these negative regulators are essential for predicting treatment response.
- Non-apoptotic cell death pathways represent a significant area for novel drug discovery.
Conclusions:
- Targeting negative regulators of cell death is a vital strategy to overcome cancer drug resistance.
- Development of predictive and response biomarkers is crucial for personalized cancer treatment.
- Non-apoptotic cell death pathways offer a promising avenue for developing novel cancer therapies and drug discovery.
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