We studied the expression of multidrug resistance genes (MDR) and monoresistance genes in normal bronchial tissue and tumor tissue of the non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy (NACT) (vinorelbine-carboplatine). The study included 30 patients with NSCLC (ТNM). Normal bronchial tissue, normal lung tissue and tumor tissue collected during surgery following neoadjuvant 2-40-30)chemotherapy (NACT) served as a material of the study. The expression levels of MDR genes ( ABCB1, ABCB2, ABCC1, ABCC2, ABCС5, ABCG1, ABCG2, GSTP and MVP, and monoresistance genes ( BRCA1, ERCC1, RRM1, TOP1, TOP2A, TUBB3 and TYMS) were estimated by quantitative reverse transcriptase PCR (RT-qPCR). The expression levels of some MDR genes and monoresistance genes ( АВСВ1, АВСВ2, ABCG1, ERCC1, GSTP1 and MVP) were significantly higher in the bronchi than in tumor tissue. The expression of ABCG1, ABCG2 and ERCC1 genes was higher in patients with Tcancer than in patients with Tcancer. Patients with adenocarcinoma had higher expression 1-2 3-4 of BRCA1, MVP and ABCB1 genes than patients with squamous cell lung cancer. A tendency towards reduction in the expression level of MDR-genes and monoresistance genes was observed in patients with partial tumor regression compared to that observed in patients with stable disease. These findings were consistent with the previous data on reduction in the MDR-gene expression after chemotherapy with a good response in breast cancer patients.
The comparative analysis of immediate and long-term clinical outcomes in 68 patients with stage III non-small cell lung cancer was carried out. The study group comprised 36 patients who received 2 cycles of neoadjuvant vinorelbin/carboplatin-containing chemotherapy with subsequent assessment of objective response. If complete and partial responses were achieved and in cases with stable disease, patients underwent radical surgery followed by 3 cycles of the same regimen of adjuvant chemotherapy. The control group consisted of 32 patients who underwent surgery alone. The results obtained showed efficacy of the combined modality treatment due to significant decrease in the rate of local recurrences, distant metastases and increase in the rate of overall survival as compared to the group with surgery alone.
The article presents a clinical case of successful simultaneous surgery for coronary artery disease and newly diagnosed apex lung tumor without postoperative complications.
In the last decade, molecularly-targeted therapy is the most intensively developing treatment modalities in oncology. The main targets for this therapy are many elements of apoptosis signaling pathways and cell cycle regulation, the damage of which is associated with a malignant growth. One of the available molecular targets is the epidermal growth factor receptor (EGFR), which activation occurs in lung cancer, colorectal cancer, squamous cell carcinoma of the head and neck , breast cancer, melanomas, etc. To block oncogenic EGFR signaling, target drug as small molecule tyrosine kinase inhibitors, peptide associated cytotoxins and antiEGFR monoclonal antibodies were created. However, there are a number of studies (FLEX, SATURN, INTEREST, IPASS), where the expected and observed clinical cure rates of target drugs are not the same, including primary goal - increasing time to tumor progression. As the cause of inconsistency of treatment results may be lack the selection of patients with the additional molecular damages (mutations or genetic polymorphisms), providing the sensitivity and /or resistance to therapeutic agent. The most important reason for discrepancy between the real and the expected treatment effect of target drugs is the phenomenon of intratumoral heterogeneity, that is manifested as coexist of cells with different biological properties, due to genetic, epigenetic, phenotypic peculiarities of tumor clones within the tumor. Search for new driver targets and the creation of drugs directed against them, development of multitarget approach are perspective to improve the effectiveness of targeted therapy. In addition, it is important to use molecular testing to monitor the treatment efficacy, because therapy can drive the tumor clonal evolution, leading to the emergence of resistant cell clones.
A case of successful surgical treatment for peripheral lung cancer with concurrent coronary artery bypass for ischemic heart disease has been presented.