Non-small cell lung cancer - mutations, targeted and combination therapy

Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis. Compounds that inhibit the activity of receptor tyrosine kinases are very well examined and already used in clinical practice. NSCLC is characterized by multiple mutations, including EGFR (epidermal growth factor receptor) and KRAS. Rarer but clinically significant is the rearrangement of the ALK gene. Currently, for NSCLC treatment a number of EGFR inhibitors such as erlotinib, gefitinib, afatinib and two compounds targeted in ALK kinase crizotinib and ceritinib are applied. Unfortunately, despite numerous studies, we are still not able to improve the treatment effectiveness of patients with KRAS mutations. The most efficient solution would be to use a combination of the compounds exhibiting synergistic effects on tumor cells. The literature data describes numerous examples of the combination treatment of NSCLC cells. Some combinations of compounds are already in clinical trials. Most attempts relate to tyrosine kinase inhibitors in combination with other types of pharmacologic inhibitor or immunotherapy. This paper describes the mutations occurring in NSCLC and drugs used in clinical practice as well as being in preclinical development.