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Updated: May 29, 2026
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils
Davide Torti1, Livio Trusolino
1Laboratory of Molecular Pharmacology, Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Candiolo (Torino), Italy.
Abstract:
A decade has elapsed since the concept of oncogene addiction was first proposed. It postulates that - despite the diverse array of genetic lesions typical of cancer - some tumours rely on one single dominant oncogene for growth and survival, so that inhibition of this specific oncogene is sufficient to halt the neoplastic phenotype. A large amount of evidence has proven the pervasive power of this notion, both in basic research and in therapeutic applications. However, in the face of such a considerable body of knowledge, the intimate molecular mechanisms mediating this phenomenon remain elusive. At the clinical level, successful translation of the oncogene addiction model into the rational and effective design of targeted therapeutics against individual oncoproteins still faces major obstacles, mainly due to the emergence of escape mechanisms and drug resistance. Here, we offer an overview of the relevant literature, encompassing both biological aspects and recent clinical insights. We discuss the key advantages and pitfalls of this concept and reconsider it as an illustrative principle to guide post-genomic cancer research and drug development.
Insights
Oncogene addiction, where cancers depend on a single dominant oncogene, shows promise but faces challenges. Understanding its molecular basis and overcoming drug resistance are key for effective cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- The concept of oncogene addiction posits that some cancers rely on a single dominant oncogene for survival.
- This notion has been supported by substantial evidence in both research and therapy.
Purpose of the Study:
- To review the literature on oncogene addiction, covering biological mechanisms and clinical applications.
- To discuss the advantages and limitations of the oncogene addiction concept.
- To re-evaluate its role in guiding cancer research and drug development.
Main Methods:
- Literature review of biological and clinical studies on oncogene addiction.
- Analysis of evidence supporting and challenging the oncogene addiction model.
- Discussion of therapeutic implications and challenges.
Main Results:
- While oncogene addiction is a powerful concept, its underlying molecular mechanisms remain incompletely understood.
- Clinical translation faces obstacles, primarily due to emergent resistance and escape mechanisms.
- The concept offers valuable insights but requires further refinement.
Conclusions:
- Oncogene addiction remains a significant principle in cancer biology and targeted therapy development.
- Further research is needed to elucidate molecular mechanisms and overcome therapeutic resistance.
- The concept serves as a crucial guide for post-genomic cancer research.
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