Search

Supplemental Digital Content is available in the text.Anlotinib is a multi-target tyrosine kinase inhibitor developed independently in China. Its biological effects remain unclear in small-cell lung cancer (SCLC). The current study aimed to evaluate the effects of anlotinib in combination with irinotecan on H446 and H2227 SCLC cell lines and provide new treatment strategy for SCLC. Cell growth of two cell lines was inhibited by anlotinib, irinotecan and the combination in a dose-dependent manner. After 72 h incubation, the inhibition rate was greater in the combination group than all single drug group. A similar result was found when apoptosis was assessed after 12 h, but not after 6 h of treatment. Compared with single drug, combination drug suppressed the migration and invasion abilities in two cell lines; however, there was no difference between individual anlotinib or irinotecan. The colony formation rate was obviously lower in the combination group. Vascular endothelial growth factor receptor, fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor were expressed in two cell lines after treatment regardless single or combination, but FGFR was expressed more after combination treatment than anlotinib. The expression of phosphorylated (p) ERK was decreased with anlotinib alone or combination treatment and pAKT expression was impaired with combination treatment, but not with anlotinib or irinotecan alone. The biological function of anlotinib and irinotecan may be mediated through the AKT/ERK signaling pathway. Additional investigations on biomarker-guided patient-stratification and elucidating individualized targets in patients anlotinib are urgently needed.

Objective: NTRK mutations and clinicopathological factors in patients with lung cancer in northeast China were analyzed by next-generation sequencing (NGS), and references were provided for patients with NTRK mutations undergoing targeted therapy in northeast China.Methods: A total of 224 specimens in 173 patients with lung cancer were collected. This included 51 patients with matched tissue and whole blood samples,133 tissue samples, 84 whole blood samples, and 7 pleural effusion samples. NGS (520 genes) was used to detected NTRK mutations and clinicopathologic factors.Results: NTRK mutation was detected in eight patients (8/173, 4.6%), including four NTRK missense mutations (4/173, 2.3%), two NTRK fusion gene mutations (2/173, 1.2%), and two NTRK copy number deletions (2/173, 1.2%). Among the eight patients with NTRK mutations, four were associated with lung cancer driver gene mutations (3/4 EGFR, 1/4ALK); NTRK in two patients was inconsistent in tissue and paired whole blood testing; NTRK missense mutation was detected in one patient, and NTRK copy number deletion was detected in the other; and NTRK wild type was detected in two patients. There was no correlation between NTRK mutation and clinicopathologic factors (including gender, age, pathological type, smoking status, metastasis site).Conclusion: NTRK mutation was only 4.6%, effective fusion gene mutation was 1.2%, and common driver gene mutation in lung cancer was evident in 50% of patients. The results of NTRK were inconsistent with matched tissues and whole blood. Therefore, patients with NTRK mutation should use a variety of specimen types and large target area sequencing (panel) analysis method to provide individualized treatment.