Thanks to the approaches of precision medicine, great strides have been made in the diagnosis and treatment of diabetes mellitus, taking into account the individual characteristics of each patient or subgroups for monogenic subtypes of diabetes and newborn diabetes. For monogenic diabetes, molecular genetics can identify discrete etiological subtypes, the manifestation of which has profound implications for treatment, and predict the further development of concomitant clinical signs that allow early prophylaxis or supportive therapy. In contrast, second-type diabetes mellitus has a polygenic nature, which makes it difficult to define discrete clinical subtypes. The implementation of the approaches of precision medicine in the diagnosis and treatment of diabetes mellitus will allow a targeted selection of drug therapy. This review shows the successful use of precision medicine in monogenic diabetes and the possibilities of this approach to solving problems in diabetes of the second type.
The purpose of the study: to conduct a systematic literature review on the effectiveness and feasibility of using information on the presence of KRAS gene mutations (in different codons), TP 53 (KP), ST K11/LKB1 (KL), and KEAP mutations and the association of KRAS m with PD -L1 status in patients with non-small cell lung cancer (NSCLC ) as a predictor of the effectiveness of immunotherapy with immune checkpoint inhibitors.Material and Methods. The review includes data from randomized clinical trials and meta-analyses on the predictive value of KRAS mutation status for response to immunotherapy in patients with NSCLC over the past 10 years.Results. The presence of KRAS mutations in NSCLC patients could be a predictive factor for their response to immunotherapy, as several studies have demonstrated benefit from immunotherapy in these patients. The combination of KRAS mutation with TP 53 (KP) co-mutation predicts a better response to immunotherapy, while a combination with ST K11/LKB1 (KL) and KEAP 1 predicts a worse response (reduced response rate and overall and disease-free survival). In PD -L1-positive patients, the presence of KRAS mutation is associated with a better prognosis after treatment with immunotherapy. Moreover, the presence of KRAS mutation is associated with a worse response to first-line and subsequent-line chemotherapy, thus indicating a more promising use of immunotherapy in these patients.Conclusion. Identification of TP 53 (KP), ST K11/LKB1 (KL), and KEAP 1 co-mutations and the presence of KRAS mutation in addition to determination PD -L expression enable selection of patients who will obtain the greatest benefit from immunotherapy. In addition, the ability to determine KRAS mutation and co-mutation status using a liquid biopsy (with acceptable specificity and sensitivity) makes it possible to use this method for determining sensitivity to immunotherapy when it is not possible to obtain tumor sample (to determine PD 1-L1 expression).
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