**3.3 Lung cancer**

Lung cancer is the primary cause of cancer-related deaths worldwide. Active and passive smoking are the two of primary causes of lung cancer. Lung cancers are classified as small cell (non-epithelial) or non-small cell carcinomas (epithelialderived). Small cell carcinomas are highly malignant; has the ability to metastasize easily and chemotherapy is the choice of treatment. However, treatment of nonsmall cell cancer primarily involves surgical excision, supplemented by radiation or chemotherapy. Although this treatment method may provide partial or full recovery, it also increases the risk for concurrent diseases. Using anti-cancer drugs with "high efficacy and low-toxicity" is the priority goal in this field [30, 31].

KRAS gene mutations are observed in 15–25% of all lung cancer cases. These mutations are more frequent in white populations than in Asian populations. About 25–50% of whites with lung cancer have KRAS gene mutations, whereas 5–15% of Asians with lung cancer have KRAS gene mutations [14].

In lung adenocarcinomas, both KRAS-activating mutations and in and EGFR mutations can be observed. KRAS appear to be mutually exclusive. Three different mutations in the KRAS gene have been associated with lung cancer [32]. Nearly all of the KRAS gene mutations associated with lung cancer change the amino acid glycine at position 12 or 13 (Gly12 or Gly13) or change the amino acid glutamine at position 61 (Gln61) in the K-Ras protein. These mutations cause a constantly activated KRAS, which directs the cells to proliferate in an uncontrolled way, and the high cellular proliferation leads to tumor formation [33].

Even though KRAS mutations were identified in non-small cell lung tumors more than 20 years ago, the clinical value of determining KRAS tumor status is recently gaining importance. Recent studies indicate that patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy and do not respond to EGFR inhibitors. There is a clear need for therapies specifically developed for patients with KRAS-mutant non-small cell lung cancers [34, 35]. KRAS gene mutations are much more common in long-term tobacco smokers with lung cancer when compared to nonsmokers. Lung cancers with KRAS gene mutations typically indicate a poor prognosis and are associated with resistance to several cancer treatments [33–35].
