months (p = 0,013). There were no significant differences in age, ECOG PS, histology, size, therapies or treatment line. Conclusions: The NLR remains a prognostic factor in both diseases, with or without EGFR mutation, but appear to have less impact on the outcome of EGFR mutated patients. In NSCLC EGFR mutated maybe inflammatory index could have implications on therapeutic choice, especially subsequent lines and his role deserves further study. Legal entity responsible for the study: Mario Scartozzi. Funding: Has not received any funding.

Background: Tumor metastasis is the main cause of death of cancer patients and the biggest hurdle for cancer cure. The identification of decisive drivers of metastasis is thus an urgent therapeutic need.Methods: Cancer cell spheroids, wound healing and cell aggregation assays were utilized to explore cell-cell adhesion capacity. Immunofluorescence confocal microscopy and flow cytometry analysis were utilized to quantify expression of target proteins, IHC analysis quantified the expression of target molecules in primary tumors and metastases. Pre-clinical models of orthotopic growth of colon cancer and metastatic diffusion to the liver were utilized. Xenotransplant transcriptome analysis assessed EMT determinant transcription. Patients: 24 distinct case series of breast, colon, uterus, ovary, stomach, lung, and pancreatic cancers, for a total number of 13,042 primary tumors were analyzed. KaplaneMeier plots were used to illustrate survival and metastatic relapse in investigated cohorts.Results: We identify functional inactivation of highly expressed E-cadherin as a pivotal driver of metastatic diffusion in human cancer. E-cadherin is inactivated by binding to Trop-2, which causes release from the cytoskeleton, loss of cell-cell adhesion and activation of b-catenin, while maintaining epithelial differentiation. This leads to antiapoptotic signaling, increased cell migration capacity and enhanced cancer cell survival. This global, Trop-2/E-cadherin/b-catenin-driven pro-metastatic program was recapitulated in human cancer, and was shown to profoundly impact on breast, colon, ovary, uterus, stomach cancer metastatic diffusion. Conclusions:We identify functional inactivation of E-cadherin by Trop-2 as a pivotal driver of EMT-less metastatic diffusion in human cancer. This global, Trop-2/E-cadherin/b-cateninedriven pro-metastatic program profoundly impacts on the survival of patients bearing breast, colon, uterus, ovary, stomach, lung, pancreas tumours, paving the way for novel diagnostic procedures and anti-cancer therapies.Legal entity responsible for the study: The authors.

Background: The emergence of platinum resistance is a significant obstacle to clinical management of lung cancer. We aimed to analyze the EGFR signaling and efficacy of EGFR inhibitors in acquired cisplatin resistance. Better understanding forms a basis for the development of novel combination therapies that could enhance patient survival. Methods: An isogenic clinical model was used to induce resistance in a panel of cell lines (H838, HCC827, H1975 and H1650 NSCLC cells) and H1339, an SCLC cell line. Cells were exposed to cisplatin (1 μg/ml/3 hrs/week) followed by recovery periods over of 4 weeks, and cisplatin-resistant phenotype (CRP) derived from original, age-matched naïve cells. They were then characterized by survival, proliferation, colony formation, and apoptosis. EGFR family receptors, phosphorylation and downstream signalling was assessed by EGFR phosphorylation and the PathScan Signaling array. The effects of EGFR TKIs (erlotinib, gefitinib, afatinib, and rociletinib) on CRP cells was evaluated at clinical concentrations. Results: CRP cells demonstrated increased survival, proliferation and resistance to apoptosis against the cisplatin challenge. CRP cells displayed altered expression of EGFR receptor family and their phosphorylation and critical nodes of signaling. But their appearance varied from cell line to cell line in comparison to their respective controls. The EGFR TKIs (except erlotinib on H838 cells) showed similar effects on CRP and their naïve cells. Conclusions: Our results identified CRP of NSCLC cells, which exhibited enhanced total EGFR and Met protein expression and their phosphorylation. This altered the expression of critical oncoproteins. The information can be used to design combination therapies with other TKIs to improve patient life. Legal entity responsible for the study: Respiratory Medicine and Thoracic Oncology (LMU Klinikum der Universitaẗ Munchen) Funding: German Center for Lung Research (DZL), Germany Disclosure: All authors have declared no conflicts of interest.