title: Predicting resistance by selection of signaling pathways.
abstract: Epidermal growth factor receptor (EGFR) mutations occur in 17% of non-small-cell lung cancer (NSCLC) patients with notable response to single agent therapy but with low complete remission rate and, eventually, disease progression. Priming BIM, a pro-apoptotic signaling BH3-only protein, induces sensitivity to erlotinib in EGFR-mutant cell lines. Synthetic lethal approaches and preemptive therapies based on the initial expression of BIM may significantly improve the treatment outcome. EGFR mutations result in transient pro-death imbalance of survival and apoptotic signaling in response to EGFR inhibition. SHP2 is essential to the balance between ERK and the phosphoinositide-3-kinase (PI3K)/AKT and signal transducer activator of transcription (STAT) activity, while mTOR can be an additional marker for patients with high BIM expression. Furthermore, stromal hepatocyte growth factor (HGF) confers EGFR tyrosine kinase inhibitor (TKI) resistance and induces interreceptor crosstalk with integrin-b4, Eph2, CUB domain-containing protein-1 (CDCP1), AXL and JAK1. Only by understanding better, and in more depth, complex cancer molecular biology will we have the information that will help us to design strategies to augment efficacy of EGFR TKIs and offer our patients the best, most correct therapeutic option.
authors: 1 Dr Rosell Oncology Institute, Quirón Dexeus University Institute, Barcelona, Spain ; 2 Pangaea Biotech, Quirón Dexeus University Institute, Barcelona, Spain ; 3 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 4 Molecular Cancer Research (MORe) Foundation, Barcelona, Spain.
authors: Niki
authors: N
authors: Karachaliou
authors: 1 Dr Rosell Oncology Institute, Quirón Dexeus University Institute, Barcelona, Spain ; 2 Pangaea Biotech, Quirón Dexeus University Institute, Barcelona, Spain ; 3 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 4 Molecular Cancer Research (MORe) Foundation, Barcelona, Spain.
authors: Rafael
authors: R
authors: Rosell
authors: 1 Dr Rosell Oncology Institute, Quirón Dexeus University Institute, Barcelona, Spain ; 2 Pangaea Biotech, Quirón Dexeus University Institute, Barcelona, Spain ; 3 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 4 Molecular Cancer Research (MORe) Foundation, Barcelona, Spain.
authors: Miguel Angel
authors: MA
authors: Molina
authors: 1 Dr Rosell Oncology Institute, Quirón Dexeus University Institute, Barcelona, Spain ; 2 Pangaea Biotech, Quirón Dexeus University Institute, Barcelona, Spain ; 3 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 4 Molecular Cancer Research (MORe) Foundation, Barcelona, Spain.
authors: Santiago
authors: S
authors: Viteri
keywords: Lung cancer; biomarkers; epidermal growth factor receptor (EGFR) mutations; signaling pathways