Possibilities of rebiopsy for molecular genetic testing in patients with EGFR+ advanced non-small cell lung cancer (NSCLC) with progression while taking tyrosine kinase inhibitors (TKI) to determine the mechanisms of resistance

Marinov Dimitar Todorovich, Laktionova Lyudmila Valentinovna, Reutova Elena Valerievna, Yudin Denis Ivanovich

Lung cancer is still one of the most serious human diseases. In latest years, the spread of this form of cancer has become epidemic, and WHO’s worst predictions for rising morbidity and mortality have been justified. At present, in most patients (60-80%) suffering from recently found non-small cell cancer (NSCLC) in Russia, it is diagnosed with stage III-IV, which requires drug treatment. Currently, this type of malignant disease is leading in mortality among other oncological pathologies in developed countries and continues to be an urgent oncology problem. The identification of the disease for the most part in developed stages, when surgical treatment is not indicated, determines the place of radiation and chemotherapy in the provision of palliative care in this category of patients. The modern tactics of medicamental treatment is based on an agreement on the need for individualized treatment. The detection of point genetic mutations and the selection of targeted medicine that affect precisely this link in the chain of pathological processes that ensure vital activity and expansive growing of the tumor allow us to achieve the desired antitumor effect and quite often significantly improve long-term treatment results. The regularities of the resistance’s formation to tyrosine kinase inhibitors (TKIs) of the erydermal growth factor (EGFR) are characterized by significant genetic and histological heterogeneity, including factors such as the amplification of MET and HER2, transformation into SCLC, the acquisition by tumor cells of signs of an epithelial-mesenchymal transfer, similarly to the appearance of secondary mutational changes. The EGFR T790M mutation is recognized in about 50% of patients who have received immunity to 1st and 2nd generation TKIs. Thus, it becomes necessary to re-obtain a sample of tumor tissue from the site of progression. The study of certain characteristics of the primary tumor, performed at the stage of early diagnosis, may not be fully informative for planning the treatment of relapse of the disease or when it progresses during therapy. The selection of methods for repeated analysis of the tumor’s characteristics during treatment is an urgent problem in the daily activities of a doctor.

Keywords:rebiopsy, resistance to TKI, common non-small cell lung cancer, NSCLC, EGFR, T790M.