Background/Objectives: Late diagnosis and inefficient treatment regimens lead to poor prognosis, with a low 5-year survival rate for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). New targeted therapeutic agents can be developed and introduced only by first discovering new driver oncogenes and with a thorough investigation of the known driver genes. The aim of the current study is to investigate the prevalence of alterations in the eight most frequently altered genes in lung cancer—BRAF, EGFR, KRAS, ALK, ROS1, HER2, PD-L1 and PIK3CA. Methods: Real-time polymerase chain reaction (RT-PCR) was used to detect KRAS and EGFR mutations, multiplex PCR and microarray hybridization for KRAS/BRAF/PIK3CA mutations. Immunohistochemical analysis was performed for the detection of ALK, HER2/NEU, ROS-1 and PD-L1 alterations. Results: Overall, 221/603 patients (36.65%) had at least one genetic alteration, of which 22 patients (3.65%) had two genetic alterations and two patients had more than two genetic alterations. Additionally, 50 patients were identified with one or more KRAS mutations (8.29%), 45 patients with EGFR mutations (7.46%), and 1.82% with PIK3CA mutations and 0.66% with BRAF mutations. Furthermore, 50% of the co-occurring alterations were either on KRAS and PIK3CA genes (3/6), on KRAS and BRAF genes (2/6, 33.33%) or on EGFR and PIK3CA genes (1/6, 16.67%), and 10.45% of the patients exhibited PD-L1 overexpression, 5.31% ALK rearrangements, and 2.36% HER2/NEU expression, with no ROS-1 rearrangements detected. Conclusions: Comprehensive testing for somatic alterations in EGFR, BRAF, KRAS, and PIK3CA is significant in guiding therapeutic decisions in lung cancer management. Such testing should be routinely conducted to establish a thorough genetic profile of lung cancers in a manner that is both time-efficient and cost-effective.

Cytokines are critical intermediaries of immune and inflammatory responses and present a central role in the pathogenesis of numerous rare diseases. Dysregulated cytokine production and signaling contribute to disease onset, progression, and clinical heterogeneity, particularly in autoinflammatory, autoimmune, genetic, and neurodegenerative disorders. They are synthesized and secreted by numerous cell types, including monocytes, T- and B- lymphocytes, dendritic cells, natural killer cells, endothelial cells, fibroblasts, and epithelial cells. Auto-inflammatory and autoimmune diseases represent two major categories of immune-mediated disorders characterized by dysregulated immune responses. Although traditionally considered distinct, increasing evidence supports a continuum between innate and adaptive immune dysfunction. Auto-inflammatory diseases are driven primarily by aberrations in the innate immune system, without significant participation of antigen-specific T cells or autoantibodies. These conditions are often associated with genetic mutations affecting inflammasome components, leading to excessive activation of inflammatory pathways. Recent advances in molecular immunology have allowed the identification of disease-specific cytokine crosses and facilitated the advance of targeted biological therapies. Future research should therefore focus on identifying reliable biomarkers for treatment stratification, understanding mechanisms of therapeutic resistance, and developing safer and more effective immunomodulatory approaches. Continued progress in cytokine biology and precision immunology is expected to substantially improve outcomes and quality of life for patients with rare autoimmune and autoinflammatory diseases. This review delivers a comprehensive overview of cytokine biology, their involvement in rare diseases, and current and emerging cytokine-targeted therapeutic strategies. Additionally, it highlights the role of cytokines as biomarkers and discusses future perspectives in precision medicine.