KRAS-mutated non-small cell lung cancer: new therapy strategies

Lung cancer remains one of the most dangerous and most common cancers, requiring constant improvement of diagnostic and treatment methods. The genetic heterogeneity of lung cancer forces us to search for new therapeutic targets in an attempt to achieve greater effectiveness for certain groups of pat...

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Main Authors: K. K. Laktionov, K. A. Sarantseva, L. A. Nelyubina, S. V. Gamayunov, E. A. Kolesnikova, M. G. Gordiev
Format: Article
Language:Russian
Published: Russian Academy of Sciences, Tomsk National Research Medical Center 2024-05-01
Series:Сибирский онкологический журнал
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Online Access:https://www.siboncoj.ru/jour/article/view/3039
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author K. K. Laktionov
K. A. Sarantseva
L. A. Nelyubina
S. V. Gamayunov
E. A. Kolesnikova
M. G. Gordiev
author_facet K. K. Laktionov
K. A. Sarantseva
L. A. Nelyubina
S. V. Gamayunov
E. A. Kolesnikova
M. G. Gordiev
author_sort K. K. Laktionov
collection DOAJ
description Lung cancer remains one of the most dangerous and most common cancers, requiring constant improvement of diagnostic and treatment methods. The genetic heterogeneity of lung cancer forces us to search for new therapeutic targets in an attempt to achieve greater effectiveness for certain groups of patients. The purpose of the study was to update current knowledge about lung adenocarcinoma with a mutation in the KRAS gene, to consider new opportunities for personalized treatment of KRAS-mutated NSCLC and to form an image of a Russian patient who is potentially indicated for targeted therapy. Material and methods. A search of available literature sources published in the Pubmed, Cochrane Library, Elibrary database was carried out, publications covering the period from 2008 to 2023 were included. Results. The article discussed molecular genetic testing, including NGS next generation sequencing, and its role in determining the presence of KRAS gene mutations in patients with lung cancer. the effectiveness of targeted drugs, such as Sotorasib and Adagrasib was also discussed. The mechanism of action is aimed at suppressing the activity of the mutant KRAS G12C protein, which can significantly improve patient survival prognosis. We obtained data on the results of testing 935 patients with non-squamous non-small cell lung cancer from various medical centers in Russia. The KRAS gene mutation was identified in 160 (17.1 %) patients, of whom 96 (10.3 %) had KRAS G12C variant. The KRAS mutation was determined by PCR in 44 patients and by NGS (including on the FoundationOne platform) in 111 patients. Clinical characteristics, such as gender, age, smoking status, PD-L1 expression level, presence of co-mutations (TP53, STK11, KEAP1, were largely similar between patients from real-world clinical practice and patients included in the CodeBreak100 study. Conclusion. The research results confirm the high effectiveness of Sotorasib and Adagrasib for patients with the KRAS G12C mutation and open up new prospects in the treatment of lung cancer. The clinical data obtained from Russian patients demonstrate consistency with the patient profile from registration studies of these drugs. This once again demonstrates the need to expand the range of molecular genetic testing for timely identification of this group of patients and prescribing the most effective treatment for them.
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spelling doaj-art-73b447e88d214b60aa826941c8d2573c2025-08-20T02:55:49ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682024-05-01232728110.21294/1814-4861-2024-23-2-72-811219KRAS-mutated non-small cell lung cancer: new therapy strategiesK. K. Laktionov0K. A. Sarantseva1L. A. Nelyubina2S. V. Gamayunov3E. A. Kolesnikova4M. G. Gordiev5N.N. Blokhin National Medical Research Center of Oncology of The Ministry of Health of Russia; N.I. Pirogov Russian National Research Medical University of the Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology of The Ministry of Health of Russia; N.I. Pirogov Russian National Research Medical University of the Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology of The Ministry of Health of RussiaNizhny Novgorod Regional Clinical Oncology CenterNizhny Novgorod Regional Clinical Oncology CenterDiagnostic Center (Center for Laboratory Research) of the Moscow Department of HealthLung cancer remains one of the most dangerous and most common cancers, requiring constant improvement of diagnostic and treatment methods. The genetic heterogeneity of lung cancer forces us to search for new therapeutic targets in an attempt to achieve greater effectiveness for certain groups of patients. The purpose of the study was to update current knowledge about lung adenocarcinoma with a mutation in the KRAS gene, to consider new opportunities for personalized treatment of KRAS-mutated NSCLC and to form an image of a Russian patient who is potentially indicated for targeted therapy. Material and methods. A search of available literature sources published in the Pubmed, Cochrane Library, Elibrary database was carried out, publications covering the period from 2008 to 2023 were included. Results. The article discussed molecular genetic testing, including NGS next generation sequencing, and its role in determining the presence of KRAS gene mutations in patients with lung cancer. the effectiveness of targeted drugs, such as Sotorasib and Adagrasib was also discussed. The mechanism of action is aimed at suppressing the activity of the mutant KRAS G12C protein, which can significantly improve patient survival prognosis. We obtained data on the results of testing 935 patients with non-squamous non-small cell lung cancer from various medical centers in Russia. The KRAS gene mutation was identified in 160 (17.1 %) patients, of whom 96 (10.3 %) had KRAS G12C variant. The KRAS mutation was determined by PCR in 44 patients and by NGS (including on the FoundationOne platform) in 111 patients. Clinical characteristics, such as gender, age, smoking status, PD-L1 expression level, presence of co-mutations (TP53, STK11, KEAP1, were largely similar between patients from real-world clinical practice and patients included in the CodeBreak100 study. Conclusion. The research results confirm the high effectiveness of Sotorasib and Adagrasib for patients with the KRAS G12C mutation and open up new prospects in the treatment of lung cancer. The clinical data obtained from Russian patients demonstrate consistency with the patient profile from registration studies of these drugs. This once again demonstrates the need to expand the range of molecular genetic testing for timely identification of this group of patients and prescribing the most effective treatment for them.https://www.siboncoj.ru/jour/article/view/3039nsclcmolecular genetic testingkraskras g12csotorasibngs
spellingShingle K. K. Laktionov
K. A. Sarantseva
L. A. Nelyubina
S. V. Gamayunov
E. A. Kolesnikova
M. G. Gordiev
KRAS-mutated non-small cell lung cancer: new therapy strategies
Сибирский онкологический журнал
nsclc
molecular genetic testing
kras
kras g12c
sotorasib
ngs
title KRAS-mutated non-small cell lung cancer: new therapy strategies
title_full KRAS-mutated non-small cell lung cancer: new therapy strategies
title_fullStr KRAS-mutated non-small cell lung cancer: new therapy strategies
title_full_unstemmed KRAS-mutated non-small cell lung cancer: new therapy strategies
title_short KRAS-mutated non-small cell lung cancer: new therapy strategies
title_sort kras mutated non small cell lung cancer new therapy strategies
topic nsclc
molecular genetic testing
kras
kras g12c
sotorasib
ngs
url https://www.siboncoj.ru/jour/article/view/3039
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AT svgamayunov krasmutatednonsmallcelllungcancernewtherapystrategies
AT eakolesnikova krasmutatednonsmallcelllungcancernewtherapystrategies
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