77P. Glycolytic marker monocarboxylate transporter 4 (MCT4) and outcome to bevacizumab (bev): An exploratory analysis in advanced non-small cell lung ...
S88 Funding: Obra Social La Caixa Foundation, Barcelona, Spain and ´ ´ also supported by a grant from the Red Tematica de Investigacion ´ Cooperativa en Cancer (RTICC; grant RD12/0036/ 0072), Spain. Disclosure: All authors have declared no conflicts of interest. 77P Glycolytic marker monocarboxylate transporter 4 (MCT4) and outcome to bevacizumab (bev): An exploratory analysis in advanced non-small cell lung cancer (A-NSCLC) L. Bonanno1 , F. Calabrese2 , A. De Paoli3 , G. Pasello1 , A. Santo4 , A. Favaretto5 , M. Chilosi6 , A. Del Conte7 , P.F. Conte8 , S. Indraccolo9 . 1 Medical Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy, 2 Department of Cardiothoracic and Vascular Sciences, Universita` degli Studi di Padova, Padua, Italy, 3 Clinical Trials and Biostatistics Unit, Istituto Oncologico Veneto IRCCS, Padua, Italy, 4 Medical Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy, 5 Medical Oncology, Ospedale Regionale Treviso, Treviso, Italy, 6 Pathology and Diagnostics, Universita` degli Studi di Verona, Verona, Italy, 7 Medical Oncology, Ospedale S. Maria degli Angeli, Pordenone, Italy, 8 Surgery,Oncology and Gastroenterology, Istituto Oncologico Veneto IRCCS, Padua, Italy, 9 Immunology and Molecular Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy Background: Platinum-based chemotherapy (CT) is the mainstay of non oncogene-addicted A-NSCLC therapy with the option of adding bev in clinically selected patients (pts). Preclinical data indicate potential effects of increased glycolytic activity on response to antiangiogenesis. MCT4 is a trans-membrane lactate transporter and is a marker of glycolytic activity. Methods: We retrospectively analyzed 125 A-NSCLCs treated with first-line platinum-based CT with/without bev. MCT4 protein expression was analyzed by immunohistochemistry. Univariate and multivariate analysis was performed to evaluate the impact of MCT4 on outcome in pts treated with/without bev. Results: The median overall survival (OS) was 11.7 (95% CI: 9.1– 15.3) months (m), the median progression free survival (PFS) was 6.7 (95% CI: 5.7–7.2) m and the response rate was 43%. Pts receiving bev were 42 (34%). MCT4 quantification was feasible in 82 (64%) cases, 28 (34%) of them were treated with bev. The impact of bev on OS and PFS found by univariate analysis was not confirmed by multivariate analysis in the study population. MCT4 expression was considered as categorical variable, dividing the population into 2 groups: tumors with high levels of MCT4 (score > 15) and tumors with null/low expression (score 0–15). MCT4 expression did not affect the outcome of the 82 pts but, re-classifying them according to treatment, a differential impact of MCT4 on outcome was noticed. Among pts receiving only CT, those expressing high MCT4 achieved a median OS of 5 (95% CI: 3.2–6.4) m versus a median OS of 11.5 (95% CI: 6.3–17.4) m in the presence of null/low MCT4 (p: 0.04). The HR was 2.1 (95% CI: 1.1–4.4) and the prognostic value was confirmed by multivariate analysis. In the CT plus bev group no effect of MCT4 on outcome was observed. Conclusions: High MCT4 expression has negative prognostic value only in pts treated with CT without bev, generating the hypothesis that bev could reverse the negative effect of increased glycolytic activity. Pts with highly glycolytic tumors might have increased benefit from bev. The results warrant further confirmation in larger retrospective cohorts with genetic profiling and prospective validation. Legal entity responsible for the study: Istituto Oncologico Veneto Funding: Istituto Oncologico Veneto Disclosure: All authors have declared no conflicts of interest.
Journal of Thoracic Oncology Vol. 11, Suppl. 4S (2016) S79–S91 78P LCRMP-1 associated aptamers inhibit tumor metastasis P.-F. Hung1 , Y.-C. Chang2 , T.-M. Hong3 , P.-C. Yang1 , S.-H. Pan4 . 1 Department of Internal Medicine, National Taiwan University NTU, College of Medicine, Taipei, Taiwan, 2 Institute of Biomedical Science, Academic Sinica, Taipei, Taiwan, 3 Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, 4 Graduate Institute of Medical Genomics and Proteomics, National Taiwan University NTU, College of Medicine, Taipei, Taiwan Background: LCRMP-1/CRMP-1 signal regulation has recently been identified as an opposing force in cancer metastasis. Our previous studies indicated that LCRMP-1 could enhance filopodia formation, cancer cell migration, and invasion via the WASP family verprolin-homologous protein-1 (WAVE-1) pathway and this phenomenon were antagonized by CRMP-1. Furtherly, we also showed the combination of high LCRMP-1 and low CRMP-1 expression predicted significantly worse overall and disease-free survival compared with low LCRMP-1 and high CRMP-1 expression in non-small cell lung cancer (NSCLC) patients. Therefore, we are interested in identification of potential molecules that can specific inhibit the function of LCRMP-1 and help clinics for NSCLC treatment. Methods: To find out functional aptamers that can specific binding to LCRMP-1 but not CRMP-1, Flag-LCRMP-1 was first immunoprecipitated from cells and used to screen specific aptamers by systematic evolution of ligands by exponential enrichment (SELEX) selection. Then, the selected pools were counter selected with Myc-CRMP-1, tested the inhibitory effects on filopodia formation and cell invasiveness, and also determined their half maximal effective concentration (EC50) in vitro. After that, we also accessed the potential inhibitory mechanism by immunoprecipitation assay in vitro and examined the potential usage to inhibit cancer metastasis in vivo. Results: Two functional LCRMP-1 antagonist aptamers, B8 and B12, were picked up from our serious selection criteria. Through invasion analysis, the EC50 values of these two aptamers were calculated as 68.5 and 73.0nM respectively. Further exploration indicated that the inhibitory mechanism of these two specific aptamers might through interrupting the binding of LCRMP-1 with WAVE-1 and actin molecules. In addition, we also observed that cells pretreated with LCRMP-1 associated aptamers could significantly inhibit cancer metastasis in vivo. Conclusions: Through SELEX selection, two specific LCRMP-1 antagonistic aptamers identified and significantly inhibit the function of LCRMP-1 on cancer metastasis. These two candidates may have the potential to develop as effective therapeutic agents for lung cancer treatment in the near future. Legal entity responsible for the study: National Taiwan University College of Medicine Funding: Ministry of Science and Technology Disclosure: All authors have declared no conflicts of interest. 79P Tiechoic acids from Staphylococcus aureus enhance cytotoxic/cytostatic influence of bimetallic complex on primary tumor culture V. Nikulina, L. Garmanchuk, N. Senchylo, T. Nikolaienko. Educational and Scientific Centre “Institute of biology”, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine Background: Ligands of Toll-like receptors (TLR) are often used as adjuvants in order to enhance the immunogenicity of vaccines in anticancer therapy. Such ligands are cell wall biopolymers of gram-positive microorganisms Staphylococcus aureus – techoic
