Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) - Volume 20, Issue 3, 2023

Exosomes and other extracellular vesicles (EVs) have emerged as versatile agents facilitating cell-to-cell communication, assuming pivotal roles in both physiological and pathological contexts. This manuscript presents an extensive overview of the existing knowledge concerning the utilization of exosomes and EVs in gene therapy and personalized healthcare. It delves into their inherent capacity for transferring genetic material, their limited immunogenicity, and their potential for precise and targeted delivery. Furthermore, the paper investigates the ever-evolving domain of biomarker discovery, where exosomes and EVs hold substantial promise for the early detection of diseases and the monitoring of treatment responses. As ongoing research advances, the manuscript explores the potential for refining protocols related to standardization and quality control, along with the optimization of scalable manufacturing methods. Additionally, the manuscript sheds light on the burgeoning potential for individualized treatments driven by genomic profiling. By examining these facets, we foresee that exosomes and EVs will play a pioneering role in ushering in a new era of precision medicine, offering safer, more efficacious, and highly customized therapeutic interventions across a spectrum of medical conditions.

Lung cancer, primarily Non-Small Cell Lung Cancer (NSCLC), is a global public health concern responsible for 80-85% of cases, with over two million new cases occurring annually, and 50% of them in Asia. While there has been a gradual reduction in United States (US) cases over the last decade, with 238,340 new cases and 127,070 deaths reported in 2023, managing metastatic NSCLC remains crucial, focusing on prolonging survival and enhancing quality of life. Integration of early palliative care shows promise in this regard. International guidelines recommend personalized treatment guided by genetic mutations (Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase, C-Ros oncogene [1ROS1]) and systemic therapies, including chemotherapy, targeted therapy, and immunotherapy, which play pivotal roles in redefining care. Treatment effectiveness hinges on factors such as cancer stage, patient health, and therapy type, with surgery and radiation therapy common in early stages and advanced stages requiring chemotherapy, targeted therapy, or immunotherapy. Despite advancements in treatment modalities, NSCLC continues to pose a significant challenge globally, particularly in Asia, where a substantial portion of new cases arise. While there has been an uncertain reduction in the incidence of lung cancer in the US over the past decade, the burden of the disease persists, with substantial mortality rates reported annually. Additionally, upon diagnosis, many NSCLC patients present with distant metastases, necessitating effective treatment strategies to improve overall survival and quality of life. The objectives include investigating targeted treatments for NSCLC with specific genetic mutations, examining mechanisms of novel therapies under study, evaluating preclinical and clinical studies for therapy efficacy and safety, identifying genetic and epigenetic biomarkers for diagnosis, prognosis, and treatment selection, developing predictive models for lung cancer recurrence and survival, assessing the efficacy of treatment approaches for early-stage lung cancer, and enhancing patient outcomes through collaborative care and lifestyle interventions. These collective efforts promise to improve patient outcomes and quality of life in the battle against NSCLC.

Background: Migraine is one of the most common diseases that significantly impairs the quality of life. This condition has a pronounced genetic component. Genes responsible for the development of monogenic forms of hemiplegic migraine have already been identified, and the search for genetic associations with common migraine and its subtypes continues. Objective: The aim of this study was to search for new potential genetic markers of migraine by analyzing available open genetic databases. Methods: The analysis included databases such as ClinVar, GWAS Catalog, UK Biobank and FinnGen. In all databases, the keyword "migraine" was used to search for migraineassociated variants. Genetic variants with clinical annotations "pathogenic" and "likely pathogenic" were selected from the variants in the ClinVar database. From other databases, variants with an association significance level of p ≤ 5×10^-8 were chosen. Results: A total of 112 genetic variants associated with migraine were identified. After excluding polymorphisms known from previous migraine studies, it was found that 45 genetic variants were identified for the first time. Conclusion: These variants belong to various functional groups, including ion channels, enzymes, receptors, and regulatory proteins, confirming the current understanding of the polygenic nature of migraine. Identifying new genetic associations with migraine can contribute to a better understanding of its pathogenesis and open new possibilities for diagnosis and the development of more effective treatment strategies for this condition.

Background: Pneumonia is one of the most common complications of the course of COVID-19. Interferon-γ (IFN-γ) is an essential cytokine for lung defense against intracellular and extracellular pathogens. Since the rs2430561 variant of the IFNG gene, which encodes IFN-γ, affects the production of IFN-γ, it can potentially be associated with a severe course of COVID-19. Objective: The aim of our research was to determine the impact of the rs2430561 variant of the IFNG gene on the propensity of patients to develop and experience a severe course of COVID-19-related pneumonia. Methods: The study included 117 patients with a complicated course of COVID-19- associated pneumonia, who were hospitalized in the intensive care unit. All patients received a standard clinical and laboratory evaluation and course of treatment for COVID- 19. IFNG gene variants were determined by PCR method. For comparisons, we used clinical and laboratory indicators from the inpatients’ medical records, which reflected the course of the patient's disease, taking into account the rs2430561 variants of the IFNG gene. Results: In the group of patients, the following genotype frequencies were found: TT – 18.8%, TA – 52.1%, and AA – 29.1%. The results showed that AA genotype carriers had essentially higher SpO2/FiO2 ratio (p=0.043). High base excess rates were present in patients with the TT genotype (p=0.047). It was found that patients with the T allele (whether homozygous or heterozygous state) had significantly higher concentrations of such electrolytes as potassium and sodium (p=0.016 and p=0.004, respectively). Сonclusion: In patients with COVID-19, the rs2430561 variant of the IFNG gene is linked to a complicated course of pneumonia. Certainly, this finding requires further research.