Abstract 2947: MicroRNA 10b, 27a and 27b are involved in the resistance to treatment with epidermal growth factor tyrosine inhibitor (EGFR-TKI) in EGFR mutant lung cancer cell line

Abstract

Abstract EGFR TKIs are now standard of care in lung cancer patients with EGFR mutation. Invariably, these patients develop resistance and require treatment with another EGFR TKI or chemotherapy. The gate-keeper mutation T790M is responsible for about 50% of resistance. Rocelitinib(R) is a third generation EGFR TKI active in lung cancer cells with T790M mutation. Other mechanisms may also confer resistance in these patients. High expression of microRNA (miR)-10 is associated with worse prognosis in resected lung cancer patients with EGFR mutation. Both miR-27a and 27b are associated with increased expression of c-met which is a potential mechanism of resistance to EGFR TKI. We hypothesized that miR 10b and 27a and 27b modulate resistance in E-resistant lung cancer cells. Material and Methods Lung cancer cell lines with EGFR mutation HCC827 and HCC4006 were treated with 5 nM of Erlotinib (E) for 72 hours. E-resistant cells were then treated with R at 21.5 nM for 72h. The cells were harvested and microRNA profiling was performed by real time PCR. HTB177 cell line without EGFR mutation was used as control. Results We observed increased expression of miR-10b and miR-27a in HCC4006 compared to control cells HTB 177 cells; miR-27b is upregulated in HCC827 cell line. The increased expression of miR-10b and miR 27a were higher in CRL-2871 than the control cells 9-fold and 8-fold, respectively. MicroRNA- 27b was increased 300-fold in HCC827 compared with control. Treatment with R reduced the proliferation in HCC827 to 30% and in HCC4006 to 50% compared to control. It did not inhibit the proliferation of HTB177 cells. R increase miR-10b in HCC4006 by 3-fold, miR-27a by 1.5-fold; in HCC827 it reduced miR-10b to 0.4, miR-27a to 0.4 and miR-27B 0.5. Conclusion We observed upregulation of miR-10b, 27a and 27b in lung cancer cells lines with EGFR mutation that were resistant to E treatment. Treatment of E resistant cells with R reduced proliferation and changed the expression of miR-10b, 27a and 27b. Our results suggest an epigenetic mechanism of resistance in addition to the T790M mutation. MicroRNAs may be studied as targets for developing novel approach for to treating patients with EGFR TKI resistance. Citation Format: Hannah Montes, Emma B D Reyes, Mukut Sharma, Chao H. Huang. MicroRNA 10b, 27a and 27b are involved in the resistance to treatment with epidermal growth factor tyrosine inhibitor (EGFR-TKI) in EGFR mutant lung cancer cell line. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2947.