Predictive value of the KRAS gene mutation variant and co-mutation status when using immunotherapy in patients with non-small cell lung cancer

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Abstract

Background. Predicting the disease course and response to various types of drug therapy is an important aspect of treating non-small cell lung cancer (NSCLC). With the rapid development of various molecular genetic testing options, particularly next-generation sequencing, it has become possible to obtain data on a large number of genetic abnormalities simultaneously. This wealth of information on the molecular genetic characteristics of tumors has become available for analysis and subsequent synthesis of data regarding the effectiveness of specific systemic therapies in each individual case, depending on the patient’s mutation status.

Aim. To evaluate the impact of KRAS mutations, such as KRAS G12C, G12D, G12V, and G12A, as well as the most common co-mutations with KRAS, on the effectiveness of immunotherapy in the treatment of lung adenocarcinoma.

Materials and methods. Collection and analysis of data from foreign and domestic literature on the prognostic significance of the comutation status of patients with KRAS-mutated NSCLC, mainly over the past 5 years. Sources were searched in the PubMed, Cochrane Library, and eLibrary abstract databases. Detailed information on the prognostic significance of the co-mutation status of patients with KRAS-mutated NSCLC is presented. It has been shown that different KRAS mutations, along with various co-mutations, have different impacts on the efficacy of immunotherapy, making expanded genetic testing of NSCLC a relevant and in-demand task with practical application.

Conclusion. Determining the co-mutation status of NSCLC patients, particularly the KRAS gene status in combination with other mutations such as TP53, STK11, KEAP1, and others, is crucial for determining sensitivity to immunotherapy and prognosticating the disease course. This field is actively developing both in Russia and internationally, demonstrating its potential and potential practical application.

About the authors

Aleksey M. Kazakov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: Kazakovich873@gmail.com
ORCID iD: 0000-0002-9534-2729
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Marat G. Gordiev

Moscow Scientific and Practical Center for Laboratory Research of the Moscow City Health Department

Email: Kazakovich873@gmail.com
ORCID iD: 0000-0002-3848-865X
Russian Federation, Build. 1, 49 Orekhovy Boulevard, Moscow 115580

Konstantin K. Laktionov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; N.I. Pirogov Russian National Research Medical University (Pirogov University), Ministry of Health of Russia

Email: Kazakovich873@gmail.com
ORCID iD: 0000-0003-4469-502X
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522; Build. 6, 1 Ostrovityanova St., Moscow 117513

Svetlana Yu. Kruteleva

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: Kazakovich873@gmail.com
ORCID iD: 0000-0002-4573-8477
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Daria D. Tkacheva

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: Kazakovich873@gmail.com
ORCID iD: 0009-0003-8591-9947
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

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