DOI: 10.18413/2658-6533-2022-8-2-0-3

Germline mutations as possible biomarkers of immune checkpoint inhibitor therapy efficacy in patients with renal cell carcinoma (mini review)

Background: The use of immune checkpoint inhibitors (ICIs) is a promising therapy in cancer treatment, in particular renal cell carcinoma (RCC). Despite the revolutionary breakthrough in cancer treatment, a significant part of patients is resistant to ICIs. To date, the assessment of the PD-L1 protein expression level (programmed cell death receptor 1 ligand) on tumor cells is the only approved method for prescribing ICI therapy, however, this marker does not accurately predict the response to therapy. In this regard, the search for additional prognostic factors to control the treatment success of patients with ICI drugs based on complex genetic and epigenetic analysis is relevant. The aim of the study: To analyze and summarize the results of molecular genetic studies for the purpose of possible use as efficacy prognostic biomarkers when prescribing ICT drugs. Materials and methods: The review and analysis of Russian and foreign literature in the Pubmed, Scopus, Google Academy, Elibrary databases over the past 5 years was performed based on existing studies that allow to evaluate the possible effects of genetic polymorphisms on the ICI therapy efficacy and the resistance development. Results: Germline mutations in genes associated with the tumor microenvironment and PD-1, CTLA-4 genes, as well as heterozygous carriage of the human leukocyte antigen class I (HLA-I) gene were associated with improved efficacy and survival rates in patients receiving ICI therapy. Despite the relevant problem of the existing biomarkers failure in the immunotherapy administration, the role of molecular genetic features of cancer patients has been underexplored and requires further research in this area. Conclusion: Molecular genetic characteristics of patients play an important role in the therapy response, including antitumor therapy. The use of additional prognostic markers for ICIs therapy efficacy in patients with different tumor types will make it possible to personalize the approach in cancer treatment, increase the accuracy of candidate selection and reduce the risk of immune-mediated adverse events

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