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Reversible Myc hypomorphism identifies a key Myc-dependency in early cancer evolution
Nicole M Sodir1,2, Luca Pellegrinet3, Roderik M Kortlever3
1Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK. sodirn@gene.com.
Nature Communications
|November 9, 2022
Summary
Reducing Myc expression in adult mice significantly blocks cancer progression, including lung and pancreatic cancers. This Myc hypomorphism prevents tumor evolution by hindering microenvironmental support, with manageable side effects.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Germ-line Myc hypomorphism in mice delays cancer onset and causes mild pathologies.
- Myc is a crucial transcription factor involved in cell growth and proliferation.
Purpose of the Study:
- To investigate if acute Myc hypomorphism in adult mice can prevent tumor progression.
- To determine the mechanisms by which Myc hypomorphism inhibits cancer development.
Main Methods:
- Utilized a genetically engineered mouse model for inducible and reversible Myc hypomorphism.
- Induced Myc hypomorphism in adult mice with established KRasG12D-driven lung and pancreatic cancers.
Main Results:
- Adult Myc hypomorphism profoundly blocked KRasG12D-driven lung and pancreatic cancers.
- Cancer progression was arrested at the pre-tumoral stage due to impaired microenvironmental remodeling signals.
- Mild side effects, mainly in hematopoiesis, were observed but could be circumvented with metronomic hypomorphism.
Conclusions:
- Acute Myc hypomorphism in adult mice is a potent strategy for blocking cancer progression.
- Myc hypomorphism inhibits invasive cancer by disrupting essential microenvironmental support signals.
- Reversible Myc hypomorphism offers a promising therapeutic approach with manageable side effects.
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