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Testing Nature's Defenses: Inducing Cancer in the Naked Mole Rat

Amy M Boddy1, Lisa M Abegglen2,3

  • 1Integrative Anthropological Sciences, University of California, Santa Barbara, Santa Barbara, California.

Cancer Discovery
|January 12, 2026
PubMed

Insights

Naked mole rats need three genetic changes for lung cancer, unlike mice which only need one. This discovery aids in understanding cancer resistance and modeling rare lung tumors.

Area of Science:

  • Oncology
  • Comparative Genomics
  • Cancer Biology

Background:

  • Murine models readily develop lung cancer from a single Eml4-Alk fusion.
  • Naked mole rats exhibit remarkable cancer resistance.
  • Understanding species-specific oncogenic drivers is crucial for cancer research.

Purpose of the Study:

  • To investigate the genetic requirements for lung tumorigenesis in naked mole rats.
  • To establish a novel inducible cancer model in naked mole rats.
  • To explore mechanisms underlying cancer resistance.

Main Methods:

  • Development of an inducible Eml4-Alk oncogene expression system in naked mole rats.
  • Simultaneous genetic manipulation to inactivate Tp53 and Rb1 tumor suppressor genes.
  • Monitoring tumor development and characterizing resulting lung carcinomas.

Main Results:

  • Naked mole rats require simultaneous Eml4-Alk, Tp53 loss, and Rb1 loss for lung cancer induction.
  • Achieved only 30% tumor penetrance even with these three oncogenic events.
  • The developed model allows for the study of resistance to multiple oncogenic drivers.

Conclusions:

  • Naked mole rats possess robust endogenous mechanisms conferring resistance to oncogenic transformation.
  • This inducible model provides a unique platform for studying cancer resistance.
  • The model is suitable for investigating rare pleomorphic lung carcinomas and potential therapeutic strategies.

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