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Updated: Jan 13, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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Why isn't an oncogenic mutation in KRAS enough to induce and sustain transformation?

Juan Iovanna1, Nelson Dusetti2

  • 1Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France; Hospital de Alta Complejidad El Cruce, Florencio Varela, Buenos Aires, Argentina; University Arturo Jauretche, Florencio Varela, Buenos Aires, Argentina.

Critical Reviews in Oncology/Hematology
|January 8, 2026
PubMed

Insights

Mutant KRAS initiates cancer by cooperating with other genetic events, not acting alone. Understanding this context is key for developing targeted cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • KRAS is a proto-oncogene encoding a GTPase regulating cell signaling pathways.
  • KRAS mutations are common in cancer but require cooperation with other genetic events for full transformation.
  • Tumor suppressor genes like p53 and p16INK4a inactivation are critical cooperating events.

Purpose of the Study:

  • To elucidate the role of KRAS mutations in cancer initiation.
  • To understand the necessity of cooperating genetic events for oncogenesis.
  • To highlight the importance of the genetic context for KRAS-driven tumorigenesis.

Main Methods:

  • Review of signaling pathways regulated by KRAS (MAPK/ERK, PI3K/AKT/mTOR, etc.).
  • Analysis of genetic cooperation required for KRAS-mediated cell transformation.
  • Examination of experimental models demonstrating oncogene-induced senescence.

Main Results:

  • KRAS mutations alone do not cause full cell transformation.
  • Cooperation with tumor suppressor inactivation is essential to overcome cellular barriers like senescence and apoptosis.
  • Mutant KRAS expression in normal cells often induces senescence, not proliferation.

Conclusions:

  • KRAS acts as an initiator, not an autonomous driver, in tumorigenesis.
  • The genetic context is crucial for KRAS-driven cancer.
  • Understanding this context is vital for developing effective, personalized cancer therapies.
Keywords:
KRASP16P53SenescenceTransformationTumor progression

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