###### Abstract  
Lung cancer is the second most frequent worldwide diagnosed cancer. Mutations in the \(RAS\) genes family are among the most common oncogenic alterations occurring in non-small cell lung cancer (NSCLC). Many treatment options against \(KRAS\) mutations have been developed for NSCLC; however, they remain insufficient. Moreover, the role of \(KRAS\) and \(HRAS\) gene expression in lung cancer remains unclear. However, inhibitors of \(RAS\) genes expression seem to be a good candidate for new drugs agents in NSCLC. This study used bioinformatical analysis to determine \(KRAS\) and \(HRAS\) gene expression and its clinical significance, and then examined the influence of three different RAS inhibitors (farnesythioslavlic acid (FTS), delatarsian and Kobe065) on cell growth and the \(KRAS\) and \(HRAS\) gene expression (by RT-qPCR) in human NSCLC A549 cells. \(KRAS\) and \(HRAS\) were shown to be overexpressed in NSCLC compared to non-tumor lung tissues of healthy individuals (from databases) and significantly associated with different clinicopathological features. It was also found that FTS, in a dose-dependent manner, suppressed proliferation of human A549 cells, while deltarasin reduced expression of \(HRAS\) in the lung cancer cells. To sum up, the results obtained from analyses based on bioinformatics databases indicate that the studied genes are potential risk factors for the development of lung cancer. On the other hand, studies of their expression on cell lines indicated that they may also be potentially important in the response to treatment using RAS inhibitors. NSCC; \(KRAS\); \(HRAS\); RAS inhibitor; farnesythioslavlic acid; deltarasin; Kobe065 202  
patients treated with molecular targeted therapy and thus requires a better understanding of intra-tumoral heterogeneity [4]. RAS proteins (HRAS, KRAS, NRAS) are members of the small GTPase family involved in cell growth, proliferation, differentiation, cell adhesion and migration [5]. Binding of a ligand to receptor tyrosine kinases (RTK), or mutations in _RAS_, leads to activation of downstream effector signaling pathways, such as RAF/MEK/ERK and PI3K/AKT/mTOR signaling cascades, which frequently determines the survival of cells [6]. Oncogenic alterations in _KRAS_, _HRAS_ and _NRAS_ genes frequently occur in lots of cancers, such as pancreatic, colorectal or lung tumors. The main cause for converting these protoocogenes into oncogenes are missense gain-of-function mutations [5], while 99% of mutations in _KRAS_ are predominant at residues G12, G13 or Q61. The major substitution in NSCLC is G12C [7]. Therefore, a lot of attention has been directed toward the role of _RAS_ family mutational status as a potential therapeutic effect in NSCLC. Mutations of _KRAS_ have been found to be negative prognostic factors for survival in NSCLC cases, as well as associated with shorter survival in advanced and at an early stage of NSCLC [6,8,9]. On the other hand, _KRAS_-mutated NSCLC is a genetically strongly heterogeneous subgroup with many co-occurring mutations (e.g., in _TP53_, _STK11_, _KEAP1_, _ATM_, _MET_, _ERBB2_, _EGFR_, _BRAF_), which might have implications in the development of treatment based on specific KRAS inhibitors [10]. In recent years, many studies have focused on using different compounds to suppress oncogenic RAS signaling, i.e., through direct inhibition of RAS, inhibition of membrane association or RAS effector signaling (RAF-MEK-ERK, PI3K-AKT-mTOR and RAL inhibitors), using synthetic lethal interactors of mutant _RAS_ or changes in RAS-driven metabolism [7]. Among numerous interesting RAS-dependent signaling inhibitors is deltarasin, a small molecular inhibitor that blocks the interaction between _KRAS_-PDE8 and disrupts oncogenic RAF/MEK/ERK and PI3K/AKT KRAS-dependent signaling. [PERSON] et al. indicate that deltarasin plays a role in reducing the binding of KRAS to the plasma membrane, a crucial process for KRAS activation function, in human ductal adenocarcinoma cell lines harboring _KRAS_ mutation.