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Updated: Aug 7, 2026
10:09
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
"Oncogenic shock": explaining oncogene addiction through differential signal attenuation
Sreenath V Sharma1, Michael A Fischbach, Daniel A Haber
1Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Summary
Oncogene addiction may be an illusion caused by differing signal decay rates after oncoprotein inactivation. This "oncogenic shock" model explains rapid cancer therapy responses and suggests new drug targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- "Oncogene addiction" describes tumor cell dependence on activated oncogenes, crucial for targeted cancer therapies.
- The underlying mechanisms of oncogene addiction are not fully understood.
- This dependence has significant implications for the efficacy and development of cancer treatments.
Purpose of the Study:
- To propose a novel mechanism explaining oncogene addiction.
- To introduce the "oncogenic shock" model for oncogene addiction.
- To identify potential new drug targets based on this model.
Main Methods:
- The study proposes a theoretical model based on signal transduction pathways.
- It analyzes the differential attenuation rates of prosurvival and proapoptotic signals.
- The model is conceptual and does not involve direct experimental procedures in this abstract.
Main Results:
- The "oncogenic shock" model suggests oncogene addiction is an illusion.
- This illusion arises from rapid decay of prosurvival signals versus slower decay of proapoptotic signals upon oncoprotein inactivation.
- Differential signal attenuation explains rapid tumor cell death after targeted therapy.
Conclusions:
- Oncogene addiction may be explained by the "oncogenic shock" phenomenon.
- This model provides a framework for understanding rapid clinical responses to targeted therapies like tyrosine kinase inhibitors.
- The model highlights potential new therapeutic targets focused on modulating oncoprotein signaling outputs.
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