72P - Differential expression profile of lung squamous cell carcinoma (LSCC) cell lines as a mean to predict drug interaction effects

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Cancer Biology
Thoracic Malignancies
Basic Scientific Principles
Presenter Alberto Verlicchi
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors A. Verlicchi1, N. Karachaliou2, C. Lazzari3, C. Codony Servat4, I. Chaib5, S. Marin5, A. Gkountakos6, S. Pilotto7, J.L. Ramírez Serrano5, R. Rosell8
  • 1Oncology, Ospedale Sta Maria delle Croci, 48121 - Ravenna/IT
  • 2Oncology, IOR, Quirón-Dexeus University Institute, 08028 - Barcelona/ES
  • 3Divisione Di Oncologica Toracica, Istituto Europeo di Oncologia - IEO, 20141 - Milano/IT
  • 4Laboratory Of Cellular And Molecular Biology, Pangaea Biotech SL, IOR Quirón-Dexeus University Institute, 08028 - Barcelona/ES
  • 5Laboratory Of Cellular And Molecular Biology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 6Laboratory Of Cellular And Molecular Biology, University of Crete, School of Medicine, 71003 - Heraklion/GR
  • 7Department Of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, 37122 - Verona/IT
  • 8Medical Oncology Service, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 08916 - Badalona/ES

Abstract

Background

LSCC, 30% of all lung cancers, still requires the validation of a reliable molecular portrait and lacks effective targeted therapies. EGFR is commonly expressed in LSCC, while FGFR1 amplification and DDR2 mutations are less common. Necitumumab, an anti-EGFR monoclonal antibody (mAb), is the only targeted therapy approved, in combination with chemotherapy, as a 1st-line treatment of metastatic LSCC patients. A major clinical challenge is that all patients who initially benefit from targeted therapies eventually develop resistance. AXL overexpression, STAT3 or YAP pathway activation, as well as hedgehog-GLI signaling have been described as mechanisms of resistance to anti-EGFR therapy. p21-activated kinase 1 (PAK1), which regulates ERK, is overexpressed in LSCC, diminishing the efficacy of anti-EGFR mAbs. Herein, we are evaluating the relevance of these pathways in LSCC cell lines, illustrating the potential for synthetic lethal approaches.

Methods

mRNA expression of AXL, STAT3, YAP, GLI2 and PAK1 were examined by quantitative real-time PCR in 6 LSCC cell lines: H2286, HCC366, H520, H1703, SK-MES-1, and EBC1.

Results

EGFR was homogeneously overexpressed in all tested cell lines, but a differential expression pattern of the other transcripts was identified. Regarding the two DDR2 mutant cell lines, the H2286 had AXL and YAP overexpression, while the HCC366 had STAT3 overexpression. The analysis of the two FGFR1 amplified cell lines demonstrated that the H1703 had STAT3 overexpression, while the H520 cells overexpressed GLI2 and PAK1. High expression of PAK1 was also detected in the p53 mutant EBC-1 cell line. The results are the mean of three independent experiments. Immunoblotting analysis is ongoing while the combined effect of necitumumab with different drugs (STAT3, PAK1, GLI and AXL inhibitors), will also be evaluated.

Conclusions

Diverse biological behavior of LSCC cancer cell lines may result from diverse underlying genetic profiles and gene expression. The awareness of these differences makes it necessary to take them into account, while planning efficient targeted strategies and synergistic drug interactions.

Clinical trial identification

Legal entity responsible for the study

Catalan Institute of Oncology Germans Trias i Pujol Health Sciences Institute and Hospital Campus Can Ruti 08916 Badalona, Barcelona Spain

Funding

This Research Project was supported by ESMO with the aid of a grant from Roche.

Disclosure

All authors have declared no conflicts of interest.