Related Experiment Video

Updated: Dec 12, 2025

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
10:13

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells

Published on: July 3, 2013

11.5K

An In Vivo Kras Allelic Series Reveals Distinct Phenotypes of Common Oncogenic Variants

Maria Paz Zafra1, Marie J Parsons2, Jangkyung Kim3

  • 1Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York. lud2005@med.cornell.edu mpz2001@med.cornell.edu.

Cancer Discovery
|August 15, 2020
PubMed

Insights

New mouse models reveal distinct effects of KRAS mutations on cancer development and differential responses to targeted therapies, advancing precision oncology for KRAS-mutant cancers.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • KRAS is a frequently mutated oncogene in various cancers.
  • Understanding specific KRAS mutations' impact on tumor initiation, progression, and therapy response is limited.

Purpose of the Study:

  • To create and characterize novel mouse models for studying KRAS mutations in lung, pancreas, and colon cancers.
  • To investigate the in vivo consequences of specific KRAS mutations and their differential sensitivity to targeted therapies.

Main Methods:

  • High-fidelity CRISPR-based engineering to generate LSL-Kras mutant mice.
  • Induction of Kras alleles in murine colon and pancreas.
  • Utilizing pancreatic organoid models for drug sensitivity testing.

Main Results:

  • Distinct quantitative and qualitative differences observed in tumor initiation driven by different KRAS mutants.
  • KRAS G13D mutants showed sensitivity to EGFR inhibition.
  • KRAS G12C mutants were responsive to covalent G12C inhibitors only with EGFR suppression.

Conclusions:

  • The developed mouse strains offer a valuable platform for in vivo KRAS biology research.
  • These models facilitate preclinical precision oncology studies for KRAS-mutant cancers.
  • Specific KRAS mutations exhibit unique cellular effects and differential therapeutic sensitivities.

More Related Videos

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity07:52

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity

Published on: November 2, 2020

6.9K
Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay10:57

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay

Published on: August 14, 2018

11.1K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.9K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.3K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.9K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.0K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K