MOLECULAR GENETIC MARKERS OF NON-SMALL CELL LUNG CANCER

Lung cancer is one of the most common oncologic diseases in the world and the most frequent cause of the death from malignant neoplasms. Last decade’s studies revealed significant number of molecular events leading to the onset and development of non-small cell lung cancer (NSCLC). Molecular profiles of various NSCLC histological types in smokers and never smokers which include differential gene expression and mutational status were identified. In lung adenocarcinoma the activation of oncogenes EGFR, KRAS, BRAF, NRAS, HER2, C-MET, PI3K, MEK1 due to gene mutations as well as EML4-ALK, ROS1, and RET due to gene translocations is of most clinical importance. Alterations in these genes are considered to be drivers triggering carcinogenesis, and mutation in the even one of them was found in 60% of the tumors. Protein products of these genes are more often the targets for the individualized targeted therapy. EGFR is the most important marker of lung adenocarcinoma, but the frequency of EGFR mutations varies depending on the ethnicity, smoking status and gender of the patient. Low molecular tyrosine kinase inhibitors specific for EGFR (erlotinib, gefitinib, afatinib) and EML4-ALK, c–MET, ROS1 (crisotinib) are the most often drugs of choice in patients with corresponding genes’ mutations. Genes involved in carcinogenesis in squamous cell lung cancer are less studied, and the activation of FGFR1, PI3K, DDR2, SOX genes may be of the most clinical value. The number of potential therapeutic targets increases constantly with the development of new technologies that discloses new mechanisms of carcinogenesis. In the future the study of molecular genetic markers should allow to perform the effective individualized therapy for patients with various types of lung cancer.