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Targeting the endoplasmic reticulum-stress response as an anticancer strategy
Sandra J M Healy1, Adrienne M Gorman, Parisa Mousavi-Shafaei
1Department of Biochemistry, National University of Ireland, Galway, Ireland.
European Journal of Pharmacology
|October 20, 2009
Summary
Cells respond to endoplasmic reticulum (ER) stress via the unfolded protein response (UPR). Targeting the UPR offers a novel anticancer strategy by inhibiting or overloading this cellular pathway.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Oncology
Background:
- The endoplasmic reticulum (ER) is crucial for protein synthesis and folding.
- Accumulation of misfolded proteins induces ER stress, linked to various diseases, including cancer.
- ER stress response, mediated by the unfolded protein response (UPR), is a key cellular survival mechanism.
Purpose of the Study:
- To review the molecular mechanisms of the UPR.
- To explore the role of ER stress in tumor growth and development.
- To analyze the potential of targeting the UPR as an anticancer strategy.
Main Methods:
- Overview of molecular pathways involved in ER stress.
- Review of evidence linking ER stress to tumor biology.
- Analysis of therapeutic strategies targeting the UPR.
- Focus on small molecule inhibitors targeting enzymatic proteins.
- Review of drugs in clinical development.
Main Results:
- ER stress is implicated in tumor growth under conditions like hypoxia and glucose deprivation.
- Two main strategies to target the UPR for cancer therapy are proposed: inhibition or overloading.
- Small molecule inhibitors targeting ER stress-related proteins are a focus for drug discovery.
- Several drugs affecting ER stress are in clinical trials for potential anti-tumor activity.
Conclusions:
- The UPR plays a significant role in tumor adaptation and survival.
- Targeting the UPR presents a promising avenue for novel cancer therapies.
- Further research and clinical development of UPR-targeting drugs are warranted for cancer treatment.
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