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Updated: Jun 25, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
Modelling oncogenic Ras/Raf signalling in the mouse
Florian A Karreth1, David A Tuveson
1Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK, Robinson Way, Cambridge, United Kingdom.
Abstract:
The Ras/Raf/MEK/ERK (or MAPK) signalling pathway relays extracellular stimuli to the nucleus, thereby regulating diverse cellular responses such as proliferation, growth, differentiation and apoptosis. Perturbation of these processes by aberrant MAPK signalling often leads to malignant transformation as indicated by the frequent occurrence in human cancers of genetic alterations affecting this pathway. In recent years, genetically modified mouse models have proven instrumental in unravelling how deregulated MAPK signalling leads to disease. Indeed, conditional activation of oncogenic K-Ras or B-Raf in mice resulted in neoplasms that closely resemble the human disease. Such tractable mouse models will enable the pursuit of basic biological mechanisms and translational applications regarding the MAPK pathway.
Insights
Aberrant Ras/Raf/MEK/ERK (MAPK) signaling drives cancer. Genetically modified mouse models mimicking human cancers are crucial for understanding MAPK pathway deregulation and developing treatments.
Area of Science:
- Molecular Biology
- Cell Signaling
- Oncology
Background:
- The Ras/Raf/MEK/ERK (MAPK) signaling pathway is critical for cellular functions.
- Dysregulation of MAPK signaling is frequently implicated in human cancers.
- Genetic alterations in the MAPK pathway contribute to malignant transformation.
Purpose of the Study:
- To investigate the role of deregulated MAPK signaling in disease development.
- To utilize genetically modified mouse models for studying cancer biology.
- To explore basic mechanisms and translational applications related to the MAPK pathway.
Main Methods:
- Conditional activation of oncogenic K-Ras in mouse models.
- Conditional activation of oncogenic B-Raf in mouse models.
- Analysis of neoplasms developed in genetically modified mice.
Main Results:
- Conditional activation of K-Ras or B-Raf led to neoplasms resembling human cancers.
- Genetically modified mouse models accurately recapitulated human disease phenotypes.
- These models provide insights into MAPK pathway-driven tumorigenesis.
Conclusions:
- Genetically modified mouse models are valuable tools for studying MAPK pathway-driven cancers.
- These models facilitate the investigation of underlying biological mechanisms.
- Translational research for MAPK pathway-related therapies can benefit from these models.
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