KRAS G12C Mutations in NSCLC: From Target to Resistance

Related Experiment Video

Updated: Nov 3, 2025

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

24.7K

Alfredo Addeo1, Giuseppe Luigi Banna2, Alex Friedlaender1,3

  • 1Swiss Cancer Center Leman, Oncology Department, Switzerland University of Geneva, University Hospital Geneva, 1205 Geneva, Switzerland.

Cancers
|June 2, 2021
PubMed

Insights

This review explores Kirsten Rat Sarcoma (KRAS) mutations in non-small cell lung cancer (NSCLC). It details KRAS biology, focusing on resistance mechanisms and their clinical impact for advanced NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lung cancer is a leading cause of cancer death globally.
  • Treatments for advanced non-small cell lung cancer (NSCLC) have improved with immune checkpoint inhibitors and targeted therapies.
  • Resistance mechanisms limit the long-term efficacy of these treatments.

Purpose of the Study:

  • To review the biology of Kirsten Rat Sarcoma (KRAS) oncogene in NSCLC.
  • To focus on primary and secondary resistance mechanisms associated with KRAS mutations.
  • To discuss the clinical implications of these resistance mechanisms.

Main Methods:

  • Literature review of KRAS mutations in NSCLC.
  • Analysis of biological mechanisms of resistance.
  • Discussion of clinical relevance and therapeutic strategies.

Main Results:

  • KRAS mutations are the most common oncogenic driver in NSCLC (20-25% of cases), predominantly in adenocarcinoma and smokers.
  • Emerging drugs show promising activity against KRAS-mutated NSCLC.
  • Understanding resistance mechanisms is crucial for improving patient outcomes.

Conclusions:

  • KRAS mutations represent a significant challenge in NSCLC treatment due to evolving resistance.
  • Further research into KRAS biology and resistance pathways is essential for developing more effective therapies.
  • Targeting KRAS and overcoming resistance mechanisms hold promise for managing advanced NSCLC.
Keywords:
KRAS G12CNSCLCadagrasibresistancesotorasib

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.0K
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.1K

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...
6.6K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.5K
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...
13.4K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K
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...
8.5K
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...
9.5K