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Updated: Jul 11, 2026

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics
Published on: January 11, 2019
Apoptosis regulators as targets for cancer therapy
1Unidad de Genética Molecular, Hospital Universitario Marqués de Valdecilla, Santander, Spain. fluna@humv.es
Abstract:
Apoptosis serves to remove excess or damaged cells and its dysregulation may lead to a number of pathological disorders including cancer. Studies during the last 20 years have unravelled much of the molecular mechanisms that control apoptosis. Whether a cell dies in response to diverse apoptotic stimuli, including DNA-damaging agents, is determined largely by interactions between proteins of the Bcl-2 family. A death signal is transmitted through the BH3-only proteins to Bax and Bak which in turn permeabilise the outer mitochondrial membrane allowing the release of apoptogenic factors, which triggers activation of cell-deathpromoting caspases. These proteolytic enzymes are tightly controlled by members of the inhibitor of apoptosis (IAP) family. Activation of the caspase cascade via cell death receptors also represents a key apoptotic pathway in both normal and tumour cells. Basic knowledge of these apoptosis regulators provides the basis for novel therapeutic strategies aimed at promoting tumour cell death or enhancing susceptibility to apoptotic inducers. This review focuses on these strategies.
Insights
Apoptosis, the process of programmed cell death, is crucial for removing damaged cells. Dysregulation of apoptosis is linked to cancer, and understanding its molecular mechanisms is key to developing new cancer therapies.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Apoptosis is essential for removing damaged or excess cells, and its dysregulation is implicated in pathological conditions like cancer.
- Over the past two decades, significant progress has been made in elucidating the molecular mechanisms governing apoptosis.
- Proteins of the Bcl-2 family play a critical role in determining cell fate by regulating the intrinsic apoptotic pathway.
Purpose of the Study:
- To review the molecular mechanisms controlling apoptosis.
- To focus on therapeutic strategies targeting apoptosis regulators for cancer treatment.
Main Methods:
- Review of scientific literature on apoptosis molecular mechanisms.
- Analysis of interactions between Bcl-2 family proteins, BH3-only proteins, Bax, Bak, caspases, and inhibitor of apoptosis (IAP) proteins.
- Examination of the caspase cascade activation via cell death receptors.
Main Results:
- The Bcl-2 family proteins mediate the transmission of death signals, leading to mitochondrial outer membrane permeabilization and the release of apoptogenic factors.
- Activation of cell-death-promoting caspases is triggered by released factors and is tightly regulated by IAP family members.
- Apoptotic pathways, including those involving cell death receptors and caspase cascades, are crucial in both normal and tumor cells.
Conclusions:
- Understanding the regulators of apoptosis provides a foundation for developing novel therapeutic strategies.
- Therapeutic strategies aim to either promote tumor cell death or enhance tumor cell susceptibility to apoptosis-inducing agents.
- Targeting apoptotic pathways offers a promising avenue for cancer treatment.
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