18P - Epithelial-to-mesenchymal transition (EMT) is required for resistance to anti-folate chemotherapy in lung cancer

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Lung and other Thoracic Tumours
Translational Research
Presenter Shunqing Liang
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors S. Liang1, T.M. Marti1, P. Dorn1, L. Froment1, S. Hall1, S. Berezowska2, G. Kocher1, R.A. Schmid1, R. Peng1
  • 1Division Of Thoracic Surgery, Inselspital Bern, 3008 - Bern/CH
  • 2Institute Of Pathology, University of Bern, 3010 - Bern/CH

Abstract

Background

Lung cancer is the leading cause of cancer lethality worldwide and non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancer cases. Although multiple therapeutic options have been developed, chemotherapy remains the first-line treatment for patients with advanced NSCLC. However, the effectiveness of chemotherapy is often limited by drug resistance and the molecular mechanisms underlying drug resistance are still poorly understood.

Methods

In this study, we investigated the cells and the underlying mechanisms that confer NSCLC resistance to chemotherapeutic agent Pemetrexed (MTA). MTA resistant cells, generated by chronical exposure to MTA of both NSCLC cell lines and primary tumor cells, were phenotypically and functionally characterized.

Results

MTA-resistant NSCLC cells featured an activated EMT, as manifested by significant upregulation of EMT-related factors. In addition, an experimentally induced EMT, by treatment with TGFβ, rendered the otherwise non-resistant NSCLC cells to be refractory to MTA. In concord, pharmacological inhibition of EMT overcomes NSCLC resistance to MTA. The same principle holds true with primary NSCLC cells. Thus, EMT is required for NSCLC resistance to anti-folate chemotherapy and blocking EMT constitutes a promising avenue to enhance the efficacy of MTA-based chemotherapy.

Conclusions

EMT accounts for resistance to anti-folate chemotherapy in NSCLC and blocking EMT overcomes the resistance phenomenon.

Clinical trial identification

Legal entity responsible for the study

Shunqing Liang

Funding

Inselspital

Disclosure

All authors have declared no conflicts of interest.