Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

Objective:To compare the therapeutic and adverse effects of chemotherapeutic regimen based on three drugs (taxol+carboplatin/cisplatin+etoposide) and two drugs (carboplatin/cisplatin+etoposide) on the combined small cell lung cancer (CSCLC). Methods:A retrospective study was conducted based on the data of 62 CSCLC patients who were admitted to and treated at Tianjin Medical University Cancer Institute and Hospital between July 2000 and April 2013. Of the 62 patients, 19 received the three-drug regi-men and 43 received the two-drug regimen. All patients received at least two cycles of chemotherapy and completed follow-up proce-dures. For each patient, the therapeutic efficacy was evaluated every two cycles, and toxicity was evaluated every cycle. Results:The response rates between the three-drug and two-drug groups were statistically significant (90%vs. 53%, P=0.033). However, no statisti-cal differences were observed in the disease control rate between the two groups (100% vs. 86%, P=0.212). The three-drug regimen could induce a better median progression-free survival compared with the two-drug regimen, but with no statistical significance (10.5%vs. 9.8%, P=0.484). Similarly, no statistical differences were noted in the median overall survival between the three-drug and two-drug groups (24.0%vs. 17.5%, P=0.457). The incidence rates of grade IV bone marrow depression and the termination of the original regi-men owing to severe adverse reactions were both significantly higher in the three-drug group than in the two-drug group (26.3% vs. 7.0%, P=0.036;31.6%vs. 14.7%, P=0.004). Conclusion:The two-drug regimen had almost the same survival rate and lower toxicity compared with the three-drug regimen. When using the TEP/TCE regimen, a close attention should be focused on its adverse reactions. The findings of this work showed that the two-agent regimen should be one of the standard treatments for CSCLC.