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Targeting endoplasmic reticulum stress for cancer therapy
1Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. schontha@usc.edu
Frontiers in Bioscience (Scholar Edition)
|December 29, 2011
Summary
The endoplasmic reticulum (ER) stress response aids cell survival but can trigger cell death when severe. Cancer cells exploit ER stress for survival, offering a therapeutic target to induce apoptosis.
Area of Science:
- Cellular Biology
- Oncology
- Molecular Mechanisms
Background:
- The endoplasmic reticulum (ER) stress response and autophagy are adaptive survival mechanisms.
- These systems can trigger programmed cell death (apoptosis) under severe stress.
- Cancer cells chronically activate ER stress pathways for proliferation and survival, even during chemotherapy.
Purpose of the Study:
- To review the principles of targeting tumor-specific ER stress for cancer therapy.
- To discuss how to exploit the pro-survival ER stress pathways in cancer cells.
- To present pharmacological agents that aggravate ER stress to induce cancer cell death.
Main Methods:
- Review of existing literature on ER stress, autophagy, and cancer.
- Analysis of the role of ER stress in tumor microenvironments and chemotherapy resistance.
- Identification and discussion of pharmacological agents that induce ER stress.
Main Results:
- ER stress response is chronically activated in tumor cells, supporting proliferation.
- This chronic activation presents a therapeutic vulnerability.
- Targeting ER stress can shift the balance from pro-survival to pro-apoptotic pathways in cancer cells.
Conclusions:
- Exploiting tumor-specific ER stress is a promising new cancer therapeutic strategy.
- Therapeutic regimens can aggravate ER stress to trigger cancer cell apoptosis.
- Pharmacological agents offer a means to exploit this pathway for cancer treatment.
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