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Published on: January 11, 2019
Cell death pathways: molecular mechanisms and therapeutic targets for cancer
Shaohui Wang1, Sa Guo2, Jing Guo3
1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine Chengdu University of Traditional Chinese Medicine Chengdu China.
Abstract:
Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in-depth exploration within this scientific domain.
Insights
Targeting cell death pathways like apoptosis and ferroptosis offers new cancer therapies. Understanding these mechanisms, including genetic factors and tumor microenvironments, is key to overcoming drug resistance and improving patient outcomes.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Cell death regulation is crucial for tissue homeostasis; its dysregulation is implicated in cancer.
- Diverse cell death pathways, including apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis, are critical in cancer development.
Purpose of the Study:
- To review and analyze the precise targeting of distinct cell death pathways for cancer therapy.
- To explore the influence of genetic, epigenetic, and microenvironmental factors on cancer cell death.
Main Methods:
- Comprehensive literature review of cell death mechanisms and therapeutic strategies.
- Analysis of signaling pathways (e.g., PI3K/AKT/mTOR, MAPK/ERK) regulating cell death.
- Examination of the tumor microenvironment's role, including hypoxia and immune interactions.
Main Results:
- Identified key cell death pathways and their dysregulation in cancer.
- Highlighted the impact of genetic/epigenetic factors and signaling cascades on cell death.
- Discussed therapeutic agents like BH3 mimetics, TRAIL, and chloroquine, and novel inducers of ferroptosis and pyroptosis.
Conclusions:
- Targeting cell death pathways presents promising therapeutic strategies for cancer.
- Multifaceted approaches are necessary to overcome tumor heterogeneity and drug resistance.
- Further research into precise targeting of cell death mechanisms holds significant clinical potential.
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