Background:

Deregulating cellular energetics is one promising hallmark of cancer and Thioredoxin reductases 1 (TrxR1) plays a key role in cell metabolism [1-4]. It was found in our previous study that the activity of TrxR1 in serum is significantly higher in cancer patients than volunteers (based on 1122 cancer patients VS 84 volunteers), and over expression of TrxR1 correlates with poor prognosis in metastatic EGFR wild-type non-small-cell lung cancer patients treated with standard 1st line platinum doublets [5]. Yet the role of TrxR1 remained unclear in metastatic non-small-cell lung cancer harboring EGFR sensitive mutation treated with standard 1st line erlotinib.

Aim:

to explore the prognostic role of TrxR1 in metastatic non-small-cell lung cancer harboring EGFR sensitive mutation treated with 1st line erlotinib.

Methods:

We have built several cohorts to explore the clinical significance of TrxR1. In this prospective observational study, 37 metastatic non-small-cell patients harboring EGFR 19 deletion or L858 mutation were recruited from cohorts of NCT01980212, NCT01991418 and NCT02098954. EGFR mutation status was test by ARMS. The activity of serum TrxR1 was measured by ELISA assay after receiving one month first line standard EGFR-TKI (erlotinib). The cut off value was set as 12. Survival data were collected and analyzed to TrxR1 levels.

Results:

Until Nov.2015, all of the 37 patients are alive. Progression free survival (PFS) was not mature yet. Follow-up data and dynamic changes of TrxR1 were in process. Among the 17 patients who progressed, survival data analysis showed that the lower TrxR1 activity group was with significantly longer PFS compared to the higher group (15.2m vs 7.0m, p = 0.029)to both mutation types, also to the exon19del subtype(17.0m vs 13.0m, p = 0.19) and to the exon 21L858R subtype(11.5m vs 4.5m, p = 0.096).

Conclusions:

High activity of TrxR1 may suggest an independent role of poor prognosis in EGFR mutation-positive advanced NSCLC treated with 1st line erlotinib, including both exon19del and L858R mutation subtypes, which helps to illustrate the different results of erlotinib treatment. Possibly, those with high TrxR1 should be given a complex of EGFR-TKI plus TrxR1 inhibition. Several inhibitors are under developed in various tumors and hopefully our study could contribute to improve the current standard treatment of lung cancer.

[1]Douglas Hanahan et al; Cell. 2011 Mar 4;144(5):646-74.

[2]Lincoln DT et al; Anti-cancer Res. 2003, 23(3B):2425-33.

[3]Turunen N, et al; APM IS. 2004, 112(2):123-32.

[4]Fan C, et al;. Cell Death Dis. 2014 Apr 24;5:e1191.

[5]Yongchang Zhang et al; Thirteenth Annual International Conference on Frontiers in Cancer Prevention Research, Poster Session B

Citation Format: Yongchang Zhang. Thioredoxin reductase 1: the key member in metabolism affects PFS of 1st line erlotinib to advanced non-small cell lung cancer harboring EGFR mutation-positive. [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 2262.