Title:KRAS Mutations in Lung Adenocarcinoma: Molecular and Epidemiological Characteristics, Methods for Detection, and Therapeutic Strategy Perspectives
VOLUME: 15 ISSUE: 5
Author(s):N. Guibert, M. Ilie, E. Long, V. Hofman, L. Bouhlel, P. Brest, B. Mograbi, C.H. Marquette, A. Didier, J. Mazieres and P. Hofman
Affiliation:Laboratoire de Pathologie Clinique et Experimentale, Hopital Pasteur, CHU de Nice, 30 avenue de la Voie Romaine, F-06002 Nice Cedex 1, France.
Keywords:Clinical trials, epidemiology, KRAS mutation, lung adenocarcinoma, prognosis, personalized medicine,
targeted therapy.
Abstract:KRAS mutations are detected in over one third of lung adenocarcinomas, most
frequently in Caucasian and smoker patients. The impact of KRAS mutations on lung
adenocarcinoma prognosis is currently subject to debate, as is their impact on the response to chemotherapy
and EGFR tyrosine kinase inhibitors. The different methods for KRAS status assessment, based on
histological and cytological samples or biological fluids, offer varying sensitivities. Since no treatments are
available in clinical routine for KRAS-mutated lung cancer patients, one of the current major challenges in
thoracic oncology is developing new dedicated strategic therapies. Different molecules can be developed that
act on a post-transcriptional KRAS protein level, blocking its cytoplasmic membrane recruitment. The efficacy
of these molecules' targeting of the different signaling pathways activated by the KRAS mutation (such as the
MEK and BRAF pathways) is related to the particular KRAS mutation subtype. New therapeutic strategies are
currently focused on certain genes linked with KRAS inducing a synthetic lethal interaction. The purpose of this
work is to provide an overview of i) the recent epidemiological and molecular findings concerning KRASmutated
lung adenocarcinoma, ii) the prognostic impact of KRAS mutations, in particular during response to
treatment, iii) the available methods for detecting this mutation, and iv) the current molecules under
development for new therapeutic strategies and the clinical trials targeting this genomic alteration.
