Related Experiment Video
Updated: Dec 13, 2025
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
KRAS inhibition in non-small cell lung cancer: Past failures, new findings and upcoming challenges
Francesco Passiglia1, Umberto Malapelle2, Marzia Del Re3
1Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano (TO), Italy.
Abstract:
Despite the high prevalence of Kirsten rat sarcoma (KRAS) mutations in non-small cell lung cancer (NSCLC), for a long time it has been defined as an 'undruggable target', with precision medicine not considered as an adequate approach to treat this subgroup of patients. After several years of efforts, preliminary data from early clinical trials have recently demonstrated that direct pharmacological inhibition of KRAS p.G12C mutation is possible, emerging as an effective targeted treatment for about 10-12% of patients with advanced NSCLC, with potential relevant impact on their long-term survival and quality of life. This review reports the current status of KRAS mutations detection in the Italian real-word scenario, summarises the biological basis of KRAS inhibition in NSCLC and provides an updated overview of therapeutic strategies, discussing the potential reasons for past failures and analysing the upcoming challenges related to the advent of new targeted agents in clinical practice.
Insights
Targeting Kirsten rat sarcoma (KRAS) mutations in non-small cell lung cancer (NSCLC) is now a reality. Direct inhibition of KRAS p.G12C offers a new targeted treatment for advanced NSCLC patients, improving survival.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Kirsten rat sarcoma (KRAS) mutations are common in non-small cell lung cancer (NSCLC), historically considered undruggable.
- Precision medicine approaches were limited for KRAS-mutated NSCLC patients.
Purpose of the Study:
- To review the current status of KRAS mutation detection in Italy.
- To summarize the biological basis for KRAS inhibition in NSCLC.
- To provide an overview of therapeutic strategies and future challenges.
Main Methods:
- Literature review of clinical trials and real-world data.
- Analysis of biological mechanisms of KRAS inhibition.
- Discussion of therapeutic strategies and challenges.
Main Results:
- Preliminary clinical trial data show direct pharmacological inhibition of KRAS p.G12C is effective.
- This targeted treatment benefits approximately 10-12% of advanced NSCLC patients.
- Potential for improved long-term survival and quality of life.
Conclusions:
- Targeted therapy for KRAS p.G12C-mutated NSCLC is a significant advancement.
- Real-world KRAS mutation detection and treatment strategies are evolving.
- New targeted agents present opportunities and challenges for clinical practice.
More Related Videos
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
