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Drug Insight: cancer therapy strategies based on restoration of endogenous cell death mechanisms
Abstract
Cell death is a normal facet of human physiology, ensuring tissue homeostasis by offsetting cell production with cell demise. Neoplasms arise in part because of defects in physiological cell death mechanisms, contributing to pathological cell expansion. Defects in normal cell death pathways also contribute to cancer progression by permitting progressively aberrant cell behaviors, while also desensitizing tumor cells to immune-mediated attack, radiation, and chemotherapy. Through basic research, much has been learned about the molecular mechanisms responsible for cell turnover and how tumors escape cell death. By exploiting this knowledge base, several innovative strategies for eradicating malignancies have materialized that are based on restoration of natural pathways for cell autodestruction. Some of these strategies have advanced into human clinical trials. Several of the current strategies based on targeting core components of the cell death machinery for cancer therapy are reviewed here, and a summary of progress toward clinical applications is provided.
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“The first approach is based on the theory that the recognition of pathogen-associated molecular patterns (PAMPs), such as bacterial cell wall components or viral RNA, by immune cells dictates the difference between silent cell death (which occurs in the absence of a pathogen) and immunogenic cell death (which is induced by a pathogen)1.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [1]
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Metadata
- Authors
- Reed, J. C.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Reed, John C
- ORCID
- Reed, John C
- Venue
- Nature Clinical Practice Oncology
- Published
- 2006-07
- Volume
- 3
- Issue
- 7
- Pages
- 388-398
- ISSN
- 1743-4254 (ISSN-L)
- 1743-4262
- OpenAlex
- W2125192217
- Cited by
- 179
- References
- 81
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 2 · 2020: 5 · 2018: 2 · 2017: 7 · 2016: 5 · 2015: 14 · 2014: 7 · 2013: 9 · 2012: 11
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Clinical Practice Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- cancer therapy, cell death pathways, apoptosis, epigenetic regulators, gene therapy, tumor immune evasion, tumor progression, clinical trials, cell turnover
- MeSH terms
- Antineoplastic Agents, Clinical Trials as Topic, Humans, Mitochondria, Neoplasms, Signal Transduction, Cell Death, Apoptosis, Apoptosis Regulatory Proteins, Inhibitor of Apoptosis Proteins, TNF-Related Apoptosis-Inducing Ligand
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