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Your search keyword '"Michele Del Sesto"' showing total 3 results
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3 results on '"Michele Del Sesto"'

1. Biological and clinical impact of membrane EGFR expression in a subgroup of OC patients from the phase IV ovarian cancer MITO-16A/MANGO-OV2A trial

Author

Luca Forlani, Loris De Cecco, Vittorio Simeon, Biagio Paolini, Marina Bagnoli, Sabrina Chiara Cecere, Anna Spina, Eleonora Citeroni, Eliana Bignotti, Domenica Lorusso, Laura Arenare, Daniela Russo, Carmine De Angelis, Laura Ardighieri, Giosuè Scognamiglio, Michele Del Sesto, Germana Tognon, Daniela Califano, Clorinda Schettino, Paolo Chiodini, Francesco Perrone, Delia Mezzanzanica, Sandro Pignata, and Antonella Tomassetti

Subjects
Ovarian cancer, Bevacizumab, EGFR, Immunohistochemistry, Microarray, Bioinformatics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Validated prognostic biomarkers for anti-angiogenic therapy using the anti-VEGF antibody Bevacizumab in ovarian cancer (OC) patients are still an unmet clinical need. The EGFR can contribute to cancer-associated biological mechanisms in OC cells including angiogenesis, but its targeting gave disappointing results with less than 10% of OC patients treated with anti-EGFR compounds showing a positive response, likely due to a non adequate selection and stratification of EGFR-expressing OC patients. Methods EGFR membrane expression was evaluated by immunohistochemistry in a cohort of 310 OC patients from the MITO-16A/MANGO-OV2A trial, designed to identify prognostic biomarkers of survival in patients treated with first line standard chemotherapy plus bevacizumab. Statistical analyses assessed the association between EGFR and clinical prognostic factors and survival outcomes. A single sample Gene Set Enrichment-like and Ingenuity Pathway Analyses were applied to the gene expression profile of 195 OC samples from the same cohort. In an OC in vitro model, biological experiments were performed to assess specific EGFR activation. Results Based on EGFR-membrane expression, three OC subgroups of patients were identified being the subgroup with strong and homogeneous EGFR membrane localization, indicative of possible EGFR out/in signalling activation, an independent negative prognostic factor for overall survival of patients treated with an anti-angiogenic agent. This OC subgroup resulted statistically enriched of tumors of histotypes different than high grade serous lacking angiogenic molecular characteristics. At molecular level, among the EGFR-related molecular traits identified to be activated only in this patients’ subgroup the crosstalk between EGFR with other RTKs also emerged. In vitro, we also showed a functional cross-talk between EGFR and AXL RTK; upon AXL silencing, the cells resulted more sensitive to EGFR targeting with erlotinib. Conclusions Strong and homogeneous cell membrane localization of EGFR, associated with specific transcriptional traits, can be considered a prognostic biomarker in OC patients and could be useful for a better OC patients’ stratification and the identification of alternative therapeutic target/s in a personalized therapeutic approach.

Published
2023
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2. Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22)

Author

Lucia Musacchio, Daniela Califano, Michele Bartoletti, Laura Arenare, Domenica Lorusso, Nunzia Simona Losito, Gennaro Cormio, Stefano Greggi, Francesco Raspagliesi, Giorgio Valabrega, Vanda Salutari, Carmela Pisano, Anna Spina, Daniela Russo, Michele Del Sesto, Vincenzo Canzonieri, Francesco Ferraù, Gian Franco Zannoni, Vera Loizzi, Viola Ghizzoni, Claudia Casanova, Valentina Tuninetti, Monika Ducceschi, Vittoria Del Vecchio, Simona Scalone, Domenico Priolo, Francesco Perrone, Giovanni Scambia, Sandro Pignata, Musacchio, Lucia, Califano, Daniela, Bartoletti, Michele, Arenare, Laura, Lorusso, Domenica, Losito, Nunzia Simona, Cormio, Gennaro, Greggi, Stefano, Raspagliesi, Francesco, Valabrega, Giorgio, Salutari, Vanda, Pisano, Carmela, Spina, Anna, Russo, Daniela, Del Sesto, Michele, Canzonieri, Vincenzo, Ferraù, Francesco, Zannoni, Gian Franco, Loizzi, Vera, Ghizzoni, Viola, Casanova, Claudia, Tuninetti, Valentina, Ducceschi, Monika, Del Vecchio, Vittoria, Scalone, Simona, Priolo, Domenico, Perrone, Francesco, Scambia, Giovanni, and Pignata, Sandro

Subjects
Ovarian Neoplasms, Proto-Oncogene Proteins B-raf, Cancer Research, therapy, peritoneal cancer, multicenter, retrospective analysis, serous ovarian, serous ovarian cancer, Cystadenocarcinoma, Serous, Proto-Oncogene Proteins p21(ras), Oncology, MITO Group (MITO 22), Humans, Female, Prospective Studies, observational, serous ovarian, peritoneal cancer, multicenter, observational, retrospective analysis, MITO Group (MITO 22), Peritoneal Neoplasms, Retrospective Studies
Abstract

Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®).A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found.MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics.This study is registered under NCT02408536 on ClinicalTrials.gov .

Published
2022

3. Evaluation of angiogenesis-related genes as prognostic biomarkers of bevacizumab treated ovarian cancer patients: Results from the phase iv mito16a/mango ov-2 translational study

Author

Gustavo Baldassarre, Nicoletta Colombo, Eliana Bignotti, Vincenzo Canzonieri, Vittorio Simeon, Paolo Chiodini, Sabrina Chiara Cecere, Gian Luca Rampioni Vinciguerra, Daniela Califano, Maria Carmela Piccirillo, Francesca Citron, Giovanni Scambia, Daniela Russo, Marco Montella, Francesco Perrone, Gian Franco Zannoni, Anna Spina, Alessandra Ciucci, Germana Tognon, Clorinda Schettino, Laura Arenare, Nunzia Simona Losito, Michele Del Sesto, Rossella De Cecio, Sandro Pignata, Gabriella Ferrandina, Piera Gargiulo, Giosuè Scognamiglio, Daniela Gallo, Simona Signoriello, Califano, D, Gallo, D, Vinciguerra, G, De Cecio, R, Arenare, L, Signoriello, S, Russo, D, Ferrandina, G, Citron, F, Losito, N, Gargiulo, P, Simeon, V, Scambia, G, Cecere, S, Montella, M, Colombo, N, Tognon, G, Bignotti, E, Zannoni, G, Canzonieri, V, Ciucci, A, Spina, A, Scognamiglio, G, Del Sesto, M, Schettino, C, Piccirillo, M, Perrone, F, Chiodini, P, Pignata, S, Baldassarre, G, Califano, D., Gallo, D., Vinciguerra, G. L. R., De Cecio, R., Arenare, L., Signoriello, S., Russo, D., Ferrandina, G., Citron, F., Losito, N. S., Gargiulo, P., Simeon, V., Scambia, G., Cecere, S. C., Montella, M., Colombo, N., Tognon, G., Bignotti, E., Zannoni, G. F., Canzonieri, V., Ciucci, A., Spina, A., Scognamiglio, G., Del Sesto, M., Schettino, C., Piccirillo, M. C., Perrone, F., Chiodini, P., Pignata, S., and Baldassarre, G.

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Angiogenesis, medicine.medical_treatment, Article, law.invention, Bevacizumab treatment, MicroRNAs, Ovarian cancer, Vessel density, Randomized controlled trial, Maintenance therapy, law, Internal medicine, Medicine, RC254-282, Chemotherapy, business.industry, Hazard ratio, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MicroRNA, medicine.disease, Angiogenesi, Settore MED/40 - GINECOLOGIA E OSTETRICIA, Biomarker (medicine), business, medicine.drug
Abstract

Simple Summary The possibility to identify, with appropriate biomarkers, patients that might mostly benefit from any given treatment is the basis of personalized oncology. Cancer biomarkers should be properly identified and validated on a large number of patients possibly enrolled in dedicated clinical trials. Here, we report the first molecular results of the MITO16A-ManGo-OV2 phase IV trial that was specifically designed to identify prognostic biomarkers of survival in epithelial ovarian cancer patients treated in first line with carboplatin-paclitaxel plus Bevacizumab (NCT01706120), a treatment for which validated predictive or prognostic biomarkers are still lacking. With this work we propose not only novel possible biomarkers for Bevacizumab-treated patients but also a way through which they can be properly collected, analyzed and statistically evaluated in the frame of large multicenter clinical trials. Abstract Background. Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment. Methods. Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes. Results. High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients’ survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance. Conclusions. The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.

Published
2021

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