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154 results on '"Claudio Isella"'

1. Dual <scp>VEGFA</scp> / <scp>BRAF</scp> targeting boosts <scp>PD</scp> ‐1 blockade in melanoma through <scp>GM‐CSF</scp> ‐mediated infiltration of <scp>M1</scp> macrophages

Author

Valentina Comunanza, Chiara Gigliotti, Simona Lamba, Gabriella Doronzo, Edoardo Vallariello, Valentina Martin, Claudio Isella, Enzo Medico, Alberto Bardelli, Dario Sangiolo, Federica Di Nicolantonio, and Federico Bussolino

Subjects
Cancer Research, Oncology, Genetics, Molecular Medicine, General Medicine
Published
2023

2. Multi-label transcriptional classification of colorectal cancer reflects tumor cell population heterogeneity

Author

Silvia Cascianelli, Chiara Barbera, Alexandra Ambra Ulla, Elena Grassi, Barbara Lupo, Diego Pasini, Andrea Bertotti, Livio Trusolino, Enzo Medico, Claudio Isella, and Marco Masseroli

Subjects
Genetics, Molecular Medicine, Molecular Biology, Genetics (clinical)
Abstract

Background Transcriptional classification has been used to stratify colorectal cancer (CRC) into molecular subtypes with distinct biological and clinical features. However, it is not clear whether such subtypes represent discrete, mutually exclusive entities or molecular/phenotypic states with potential overlap. Therefore, we focused on the CRC Intrinsic Subtype (CRIS) classifier and evaluated whether assigning multiple CRIS subtypes to the same sample provides additional clinically and biologically relevant information. Methods A multi-label version of the CRIS classifier (multiCRIS) was applied to newly generated RNA-seq profiles from 606 CRC patient-derived xenografts (PDXs), together with human CRC bulk and single-cell RNA-seq datasets. Biological and clinical associations of single- and multi-label CRIS were compared. Finally, a machine learning-based multi-label CRIS predictor (ML2CRIS) was developed for single-sample classification. Results Surprisingly, about half of the CRC cases could be significantly assigned to more than one CRIS subtype. Single-cell RNA-seq analysis revealed that multiple CRIS membership can be a consequence of the concomitant presence of cells of different CRIS class or, less frequently, of cells with hybrid phenotype. Multi-label assignments were found to improve prediction of CRC prognosis and response to treatment. Finally, the ML2CRIS classifier was validated for retaining the same biological and clinical associations also in the context of single-sample classification. Conclusions These results show that CRIS subtypes retain their biological and clinical features even when concomitantly assigned to the same CRC sample. This approach could be potentially extended to other cancer types and classification systems.

Published
2023

3. Supplementary Table 3 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 29K

Published
2023

4. Data from The Unfolded Protein Response: A Novel Therapeutic Target for Poor Prognostic BRAF Mutant Colorectal Cancer

Author

Sandra Van Schaeybroeck, Patrick G. Johnston, Ian G. Mills, Melissa J. Labonte, Claudio Isella, Puthen V. Jithesh, Vlad Popovici, Frank Burkamp, Wendy L. Allen, Heba Emam, Jessica-Anne Weir, Hajrah Khawaja, Arman Javadi, Alaa Refaat, and Nicholas Forsythe

Abstract

BRAFV600E mutations occur in ∼10% of colorectal cancer cases, are associated with poor survival, and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition. There is an unmet need to understand the biology of poor prognostic BRAFMT colorectal cancer. We have used differential gene expression and pathway analyses of untreated stage II and stage III BRAFMT (discovery set: n = 31; validation set: n = 26) colorectal cancer, and an siRNA screen to characterize the biology underpinning the BRAFMT subgroup with poorest outcome. These analyses identified the unfolded protein response (UPR) as a novel and druggable pathway associated with the BRAFMT colorectal cancer subgroup with poorest outcome. We also found that oncogenic BRAF drives endoplasmic reticulum (ER) stress and UPR pathway activation through MEK/ERK. Furthermore, inhibition of GRP78, the master regulator of the UPR, using siRNA or small molecule inhibition, resulted in acute ER stress and apoptosis, in particular in BRAFMT colorectal cancer cells. In addition, dual targeting of protein degradation using combined Carfilzomib (proteasome inhibitor) and ACY-1215 (HDAC6-selective inhibitor) treatment resulted in marked accumulation of protein aggregates, acute ER stress, apoptosis, and therapeutic efficacy in BRAFMT in vitro and xenograft models. Mechanistically, we found that the apoptosis following combined Carfilzomib/ACY-1215 treatment is mediated through increased CHOP expression. Taken together, our findings indicate that oncogenic BRAF induces chronic ER stress and that inducers of acute ER stress could be a novel treatment strategy for poor prognostic BRAFMT colorectal cancer. Mol Cancer Ther; 17(6); 1280–90. ©2018 AACR.

Published
2023

5. Supplementary Figure 1 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 431K

Published
2023

6. Supplementary Tables S1-S4 from The Unfolded Protein Response: A Novel Therapeutic Target for Poor Prognostic BRAF Mutant Colorectal Cancer

Author

Sandra Van Schaeybroeck, Patrick G. Johnston, Ian G. Mills, Melissa J. Labonte, Claudio Isella, Puthen V. Jithesh, Vlad Popovici, Frank Burkamp, Wendy L. Allen, Heba Emam, Jessica-Anne Weir, Hajrah Khawaja, Arman Javadi, Alaa Refaat, and Nicholas Forsythe

Abstract

Table S1: Top 20 pathways identified by IPA containing genes significantly upregulated between poor and good prognostic BRAFMT stage II/III CRC in GSE39582; Table S2: Top 20 pathways identified by IPA containing genes significantly downregulated between poor and good prognostic BRAFMT stage II/III CRC in GSE39582; Table S3: Top 20 pathways identified by IPA containing genes differentially expressed between poor (disease free survival 5 years) in E-MTAB-863 and E-MTAB-864; Table S4: Results of siRNA screen in BRAFMT CRC.

Published
2023

7. Supplementary Figure 6 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 3.8MB

Published
2023

9. Supplementary Table 2 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 29K

Published
2023

10. Supplementary Figure 5 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 186K

Published
2023

11. Supplementary Table 1 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 27K

Published
2023

12. Supplementary Figure 2 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 158K

Published
2023

13. Supplementary Figure 4 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 226K

Published
2023

14. Data from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

Only a fraction of patients with metastatic colorectal cancer receive clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) antibodies, which calls for the identification of novel biomarkers for better personalized medicine. We produced large xenograft cohorts from 85 patient-derived, genetically characterized metastatic colorectal cancer samples (“xenopatients”) to discover novel determinants of therapeutic response and new oncoprotein targets. Serially passaged tumors retained the morphologic and genomic features of their original counterparts. A validation trial confirmed the robustness of this approach: xenopatients responded to the anti-EGFR antibody cetuximab with rates and extents analogous to those observed in the clinic and could be prospectively stratified as responders or nonresponders on the basis of several predictive biomarkers. Genotype–response correlations indicated HER2 amplification specifically in a subset of cetuximab-resistant, KRAS/NRAS/BRAF/PIK3CA wild-type cases. Importantly, HER2 amplification was also enriched in clinically nonresponsive KRAS wild-type patients. A proof-of-concept, multiarm study in HER2-amplified xenopatients revealed that the combined inhibition of HER2 and EGFR induced overt, long-lasting tumor regression. Our results suggest promising therapeutic opportunities in cetuximab-resistant patients with metastatic colorectal cancer, whose medical treatment in the chemorefractory setting remains an unmet clinical need.Significance: Direct transfer xenografts of tumor surgical specimens conserve the interindividual diversity and the genetic heterogeneity typical of the tumors of origin, combining the flexibility of preclinical analysis with the informative value of population-based studies. Our suite of patient-derived xenografts from metastatic colorectal carcinomas reliably mimicked disease response in humans, prospectively recapitulated biomarker-based case stratification, and identified HER2 as a predictor of resistance to anti-epidermal growth factor receptor antibodies and of response to combination therapies against HER2 and epidermal growth factor receptor in this tumor setting. Cancer Discovery; 1(6); 508–23. ©2011 AACR.Read the Commentary on this article by Ciardiello and Normanno, p. 472This article is highlighted in the In This Issue feature, p. 457

Published
2023

15. Supplementary Figure 3 from A Molecularly Annotated Platform of Patient-Derived Xenografts ('Xenopatients') Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer

Author

Livio Trusolino, Alberto Bardelli, Paolo M. Comoglio, Silvia Marsoni, Anna Sapino, Enzo Medico, Salvatore Siena, Marcello Gambacorta, Lorenzo Capussotti, Mauro Risio, Andrea Sartore-Bianchi, Emanuele Valtorta, Luca Molinaro, Alberto Pisacane, Paolo Massucco, Andrea Muratore, Nadia Russolillo, Dario Ribero, Consalvo Petti, Michela Buscarino, Federica Di Nicolantonio, Davide Corà, Claudio Isella, Davide Torti, Francesco Sassi, Francesco Galimi, Giorgia Migliardi, and Andrea Bertotti

Abstract

PDF file - 172K

Published
2023

16. Data from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Purpose: We determined the gene copy numbers for MET, for its transcriptional activator MACC1 and for its ligand hepatocyte growth factor (HGF) in liver metastases from colorectal carcinoma (mCRC). We correlated copy numbers with mRNA levels and explored whether gain and/or overexpression of MET and MACC1 predict response to anti-Met therapies. Finally, we assessed whether their genomic or transcriptional deregulation correlates with pathologic and molecular parameters of aggressive disease.Experimental Design: One hundred three mCRCs were analyzed. Copy numbers and mRNA were determined by quantitative PCR (qPCR). Thirty nine samples were implanted and expanded in NOD (nonobese diabetic)/SCID (severe combined immunodeficient) mice to generate cohorts that were treated with the Met inhibitor JNJ-38877605. In silico analysis of MACC1 targets relied on genome-wide mapping of promoter regions and on expression data from two CRC datasets.Results: No focal, high-grade amplifications of MET, MACC1, or HGF were detected. Chromosome 7 polysomy and gain of the p-arm were observed in 21% and 8% of cases, respectively, and significantly correlated with higher expression of both Met and MACC1. Met inhibition in patient-derived xenografts did not modify tumor growth. Copy number gain and overexpression of MACC1 correlated with unfavorable pathologic features better than overexpression of Met. Bioinformatic analysis of putative MACC1 targets identified elements besides Met, whose overexpression cosegregated with aggressive forms of colorectal cancer.Conclusions: Experiments in patient-derived xenografts suggest that mCRCs do not rely on Met genomic gain and/or overexpression for growth. On the basis of pathologic correlations and bioinformatic analysis, MACC1 could contribute to CRC progression through mechanisms other than or additional to Met transcriptional upregulation. Clin Cancer Res; 17(10); 3146–56. ©2011 AACR.

Published
2023

17. Supplementary Tables from High USP6NL Levels in Breast Cancer Sustain Chronic AKT Phosphorylation and GLUT1 Stability Fueling Aerobic Glycolysis

Author

Letizia Lanzetti, Anna Sapino, Pier Paolo Di Fiore, Carlos Caldas, Oscar M. Rueda, Alejandra Bruna, Salvatore Pece, Chiara Luise, Giovanni Bertalot, Claudio Isella, Nadia Ducano, Emanuela Pupo, and Daniele Avanzato

Abstract

S1-Prognostic value of USP6NL gain in the METABRIC dataset S2-Correleation of USP6NL protein expression with clinical-pathological parameters in the TMA cohort

Published
2023

21. Supplementary Data from Patient-Derived Xenografts and Matched Cell Lines Identify Pharmacogenomic Vulnerabilities in Colorectal Cancer

Author

Sabrina Arena, Alberto Bardelli, Michael Linnebacher, Federica Di Nicolantonio, Livio Trusolino, Andrea Bertotti, Mathew J. Garnett, Salvatore Siena, Andrea Sartore-Bianchi, Enzo Medico, Carlotta Cancelliere, Andrea Cassingena, Fabiane Barbosa, Luca Novara, Eugenia R. Zanella, Erika Durinikova, Pamela Arcella, Monica Montone, Claudio Isella, Gabriele Picco, Giorgio Corti, and Luca Lazzari

Abstract

Supplementary Legends and Figures

Published
2023

23. Supplementary Figure S3 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits

Author

Silvia Giordano, Adam J. Bass, Bruce M. Wollison, Samantha D. Drinan, Anwesha Nag, Aaron R. Thorner, Eirini Pectasides, Anna Sapino, Paola Cassoni, Enzo Medico, Antonino Sottile, Silvia Marsoni, Dario Ribero, Michele De Simone, Giovanni Pallabazzer, Stefano Rausei, Paolo Morgagni, Daniele Marrelli, Riccardo Rosati, Valentina Mengardo, Maria Bencivenga, Andrea Sartore-Bianchi, Salvatore Siena, Federica Morano, Filippo Pietrantonio, Sarah Molfino, Gian Luca Baiocchi, Emanuele Rausa, Giovanni Sgroi, Stefano De Pascale, Uberto Fumagalli, Rossella Reddavid, Maurizio Degiuli, Caterina Marchiò, Antonella Balsamo, Tiziana Venesio, Jessica Giordano, Daniela Conticelli, Tânia Capelôa, Marilisa Cargnelutti, Daniel Moya-Rull, Silvia Menegon, Laura D’Errico, Stefano Ughetto, Cristina Migliore, Stefania Durando, Maria Apicella, Sara E. Bellomo, Claudio Isella, and Simona Corso

Abstract

ROC curves of Lee MSI signature predicting MSI genetic status in PDXs and TCGA samples cohorts.

Published
2023

24. Supplementary Table S1 from Patient-Derived Xenografts and Matched Cell Lines Identify Pharmacogenomic Vulnerabilities in Colorectal Cancer

Author

Sabrina Arena, Alberto Bardelli, Michael Linnebacher, Federica Di Nicolantonio, Livio Trusolino, Andrea Bertotti, Mathew J. Garnett, Salvatore Siena, Andrea Sartore-Bianchi, Enzo Medico, Carlotta Cancelliere, Andrea Cassingena, Fabiane Barbosa, Luca Novara, Eugenia R. Zanella, Erika Durinikova, Pamela Arcella, Monica Montone, Claudio Isella, Gabriele Picco, Giorgio Corti, and Luca Lazzari

Abstract

Supplementary Table S1

Published
2023

26. Supplementary Table S1 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Table S1 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

27. Supplementary Table S3 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Table S3 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

29. Supplementary Table S4 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits

Author

Silvia Giordano, Adam J. Bass, Bruce M. Wollison, Samantha D. Drinan, Anwesha Nag, Aaron R. Thorner, Eirini Pectasides, Anna Sapino, Paola Cassoni, Enzo Medico, Antonino Sottile, Silvia Marsoni, Dario Ribero, Michele De Simone, Giovanni Pallabazzer, Stefano Rausei, Paolo Morgagni, Daniele Marrelli, Riccardo Rosati, Valentina Mengardo, Maria Bencivenga, Andrea Sartore-Bianchi, Salvatore Siena, Federica Morano, Filippo Pietrantonio, Sarah Molfino, Gian Luca Baiocchi, Emanuele Rausa, Giovanni Sgroi, Stefano De Pascale, Uberto Fumagalli, Rossella Reddavid, Maurizio Degiuli, Caterina Marchiò, Antonella Balsamo, Tiziana Venesio, Jessica Giordano, Daniela Conticelli, Tânia Capelôa, Marilisa Cargnelutti, Daniel Moya-Rull, Silvia Menegon, Laura D’Errico, Stefano Ughetto, Cristina Migliore, Stefania Durando, Maria Apicella, Sara E. Bellomo, Claudio Isella, and Simona Corso

Abstract

MSI status transcriptional signature and GSEA analysis performed comparing MSI vs MSS samples

Published
2023

30. Supplementary Table S3 from A Subset of Colorectal Cancers with Cross-Sensitivity to Olaparib and Oxaliplatin

Author

Alberto Bardelli, Federica Di Nicolantonio, Salvatore Siena, Sergio Abrignani, Michael Linnebacher, Silvia Marsoni, Enzo Medico, Gloria Mittica, Andrea Sartore-Bianchi, Gianluca Mauri, Alessio Amatu, Andrea Cassingena, Alice Bartolini, Claudio Isella, Carola Negrino, Carlotta Cancelliere, Massimiliano Pagani, Giuseppe Rospo, Luca Lazzari, Pamela Arcella, Annalisa Lorenzato, Mariangela Russo, Nicole M. Reilly, Monica Montone, Erika Durinikova, Giorgio Corti, and Sabrina Arena

Abstract

Supplementary Table S3

Published
2023

31. Supplementary Table S3 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits

Author

Silvia Giordano, Adam J. Bass, Bruce M. Wollison, Samantha D. Drinan, Anwesha Nag, Aaron R. Thorner, Eirini Pectasides, Anna Sapino, Paola Cassoni, Enzo Medico, Antonino Sottile, Silvia Marsoni, Dario Ribero, Michele De Simone, Giovanni Pallabazzer, Stefano Rausei, Paolo Morgagni, Daniele Marrelli, Riccardo Rosati, Valentina Mengardo, Maria Bencivenga, Andrea Sartore-Bianchi, Salvatore Siena, Federica Morano, Filippo Pietrantonio, Sarah Molfino, Gian Luca Baiocchi, Emanuele Rausa, Giovanni Sgroi, Stefano De Pascale, Uberto Fumagalli, Rossella Reddavid, Maurizio Degiuli, Caterina Marchiò, Antonella Balsamo, Tiziana Venesio, Jessica Giordano, Daniela Conticelli, Tânia Capelôa, Marilisa Cargnelutti, Daniel Moya-Rull, Silvia Menegon, Laura D’Errico, Stefano Ughetto, Cristina Migliore, Stefania Durando, Maria Apicella, Sara E. Bellomo, Claudio Isella, and Simona Corso

Abstract

GC PDXs are annotated for: CNV of HER2, EGFR, FGFR2, MET, KRAS ({greater than or equal to}8 gene copies); COSMIC Mutations/Frameshifts (Allelic frequency >0.3)

Published
2023

33. Supplementary Legends and Figures from A Subset of Colorectal Cancers with Cross-Sensitivity to Olaparib and Oxaliplatin

Author

Alberto Bardelli, Federica Di Nicolantonio, Salvatore Siena, Sergio Abrignani, Michael Linnebacher, Silvia Marsoni, Enzo Medico, Gloria Mittica, Andrea Sartore-Bianchi, Gianluca Mauri, Alessio Amatu, Andrea Cassingena, Alice Bartolini, Claudio Isella, Carola Negrino, Carlotta Cancelliere, Massimiliano Pagani, Giuseppe Rospo, Luca Lazzari, Pamela Arcella, Annalisa Lorenzato, Mariangela Russo, Nicole M. Reilly, Monica Montone, Erika Durinikova, Giorgio Corti, and Sabrina Arena

Abstract

Supplementary Legends and Figures

Published
2023

34. Supplementary Figure S1 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Figure S1 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

36. Supplementary Table S2 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Table S2 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

37. Supplementary Table S3 from Patient-Derived Xenografts and Matched Cell Lines Identify Pharmacogenomic Vulnerabilities in Colorectal Cancer

Author

Sabrina Arena, Alberto Bardelli, Michael Linnebacher, Federica Di Nicolantonio, Livio Trusolino, Andrea Bertotti, Mathew J. Garnett, Salvatore Siena, Andrea Sartore-Bianchi, Enzo Medico, Carlotta Cancelliere, Andrea Cassingena, Fabiane Barbosa, Luca Novara, Eugenia R. Zanella, Erika Durinikova, Pamela Arcella, Monica Montone, Claudio Isella, Gabriele Picco, Giorgio Corti, and Luca Lazzari

Abstract

Supplementary Table S3

Published
2023

38. Supplementary Tables S1-S5 from A Molecularly Annotated Model of Patient-Derived Colon Cancer Stem–Like Cells to Assess Genetic and Nongenetic Mechanisms of Resistance to Anti-EGFR Therapy

Author

Carla Boccaccio, Livio Trusolino, Andrea Bertotti, Paolo M. Comoglio, Enzo Medico, Sara E. Bellomo, Claudio Isella, Francesca De Bacco, Francesco Sassi, Francesca Orzan, Gigliola Reato, Elia Cipriano, Viola Bigatto, and Paolo Luraghi

Abstract

Supplementary Table-S1: Somatic mutations in xenospheres Supplementary Table-S2: Pearson's correlation values between xenospheres' and xenopatients' gene expression profiles. Supplementary Table-S3: genes affected by copy number variations, as detected by WES in xenopsheres. Supplementary Table-S4: genes affected by somatic mutations, as detected by WES in xenopsheres. Supplementary Table-S5: total number of shared and private somatic mutations and copy number variations in matched xenospheres and xenopatients.

Published
2023

39. Data from Molecular Subtyping Combined with Biological Pathway Analyses to Study Regorafenib Response in Clinically Relevant Mouse Models of Colorectal Cancer

Author

Annette T. Byrne, Jochen H.M. Prehn, Livio Trusolino, Claudio Isella, Andrea Bertotti, Diether Lambrechts, Enzo Medico, Rodrigo Dienstmann, Josep Tabernero, Guillem Argilés, Patrick Dicker, Matthias P.A. Ebert, Johannes Betge, Luise Halang, Bram Boeckx, Elodie Modave, Evy Vanderheyden, Manuela Salvucci, Eugenia R. Zanella, Francesco Sassi, Andreas U. Lindner, Niraj Khemka, Giorgia Migliardi, Alice C. O'Farrell, and Adam Lafferty

Abstract

Purpose:Regorafenib (REG) is approved for the treatment of metastatic colorectal cancer, but has modest survival benefit and associated toxicities. Robust predictive/early response biomarkers to aid patient stratification are outstanding. We have exploited biological pathway analyses in a patient-derived xenograft (PDX) trial to study REG response mechanisms and elucidate putative biomarkers.Experimental Design:Molecularly subtyped PDXs were annotated for REG response. Subtyping was based on gene expression (CMS, consensus molecular subtype) and copy-number alteration (CNA). Baseline tumor vascularization, apoptosis, and proliferation signatures were studied to identify predictive biomarkers within subtypes. Phospho-proteomic analysis was used to identify novel classifiers. Supervised RNA sequencing analysis was performed on PDXs that progressed, or did not progress, following REG treatment.Results:Improved REG response was observed in CMS4, although intra-subtype response was variable. Tumor vascularity did not correlate with outcome. In CMS4 tumors, reduced proliferation and higher sensitivity to apoptosis at baseline correlated with response. Reverse phase protein array (RPPA) analysis revealed 4 phospho-proteomic clusters, one of which was enriched with non-progressor models. A classification decision tree trained on RPPA- and CMS-based assignments discriminated non-progressors from progressors with 92% overall accuracy (97% sensitivity, 67% specificity). Supervised RNA sequencing revealed that higher basal EPHA2 expression is associated with REG resistance.Conclusions:Subtype classification systems represent canonical “termini a quo” (starting points) to support REG biomarker identification, and provide a platform to identify resistance mechanisms and novel contexts of vulnerability. Incorporating functional characterization of biological systems may optimize the biomarker identification process for multitargeted kinase inhibitors.

Published
2023

40. Supplementary Materials and Methods from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Materials and Methods from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

41. Supplementary Table S2 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits

Author

Silvia Giordano, Adam J. Bass, Bruce M. Wollison, Samantha D. Drinan, Anwesha Nag, Aaron R. Thorner, Eirini Pectasides, Anna Sapino, Paola Cassoni, Enzo Medico, Antonino Sottile, Silvia Marsoni, Dario Ribero, Michele De Simone, Giovanni Pallabazzer, Stefano Rausei, Paolo Morgagni, Daniele Marrelli, Riccardo Rosati, Valentina Mengardo, Maria Bencivenga, Andrea Sartore-Bianchi, Salvatore Siena, Federica Morano, Filippo Pietrantonio, Sarah Molfino, Gian Luca Baiocchi, Emanuele Rausa, Giovanni Sgroi, Stefano De Pascale, Uberto Fumagalli, Rossella Reddavid, Maurizio Degiuli, Caterina Marchiò, Antonella Balsamo, Tiziana Venesio, Jessica Giordano, Daniela Conticelli, Tânia Capelôa, Marilisa Cargnelutti, Daniel Moya-Rull, Silvia Menegon, Laura D’Errico, Stefano Ughetto, Cristina Migliore, Stefania Durando, Maria Apicella, Sara E. Bellomo, Claudio Isella, and Simona Corso

Abstract

Pathological characteristics related to engraftment success of gastric PDXs.

Published
2023

42. Supplementary Table S4 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Table S4 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

45. Supplementary Table S6 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Table S6 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

46. Supplementary Figure S1 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits

Author

Silvia Giordano, Adam J. Bass, Bruce M. Wollison, Samantha D. Drinan, Anwesha Nag, Aaron R. Thorner, Eirini Pectasides, Anna Sapino, Paola Cassoni, Enzo Medico, Antonino Sottile, Silvia Marsoni, Dario Ribero, Michele De Simone, Giovanni Pallabazzer, Stefano Rausei, Paolo Morgagni, Daniele Marrelli, Riccardo Rosati, Valentina Mengardo, Maria Bencivenga, Andrea Sartore-Bianchi, Salvatore Siena, Federica Morano, Filippo Pietrantonio, Sarah Molfino, Gian Luca Baiocchi, Emanuele Rausa, Giovanni Sgroi, Stefano De Pascale, Uberto Fumagalli, Rossella Reddavid, Maurizio Degiuli, Caterina Marchiò, Antonella Balsamo, Tiziana Venesio, Jessica Giordano, Daniela Conticelli, Tânia Capelôa, Marilisa Cargnelutti, Daniel Moya-Rull, Silvia Menegon, Laura D’Errico, Stefano Ughetto, Cristina Migliore, Stefania Durando, Maria Apicella, Sara E. Bellomo, Claudio Isella, and Simona Corso

Abstract

Microsatellite instability (MSI) phenotype in primary gastric tumours and their corresponding PDX/ organoid

Published
2023

48. Supplementary Table S5 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Author

Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Maria Flavia Di Renzo, Enzo Medico, Timothy Perera, Lorenzo Capussotti, Mauro Salizzoni, Mauro Risio, Bruno Torchio, Ezio David, Alberto Pisacane, Francesca Maione, Federica Gonella, Gianluca Paraluppi, Dimitrios Siatis, Paolo Massucco, Andrea Muratore, Dario Ribero, Stefania Gastaldi, Davide Corà, Claudio Isella, Francesco Sassi, Davide Torti, and Francesco Galimi

Abstract

Supplementary Table S5 from Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

Published
2023

50. Supplementary Table S1 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits

Author

Silvia Giordano, Adam J. Bass, Bruce M. Wollison, Samantha D. Drinan, Anwesha Nag, Aaron R. Thorner, Eirini Pectasides, Anna Sapino, Paola Cassoni, Enzo Medico, Antonino Sottile, Silvia Marsoni, Dario Ribero, Michele De Simone, Giovanni Pallabazzer, Stefano Rausei, Paolo Morgagni, Daniele Marrelli, Riccardo Rosati, Valentina Mengardo, Maria Bencivenga, Andrea Sartore-Bianchi, Salvatore Siena, Federica Morano, Filippo Pietrantonio, Sarah Molfino, Gian Luca Baiocchi, Emanuele Rausa, Giovanni Sgroi, Stefano De Pascale, Uberto Fumagalli, Rossella Reddavid, Maurizio Degiuli, Caterina Marchiò, Antonella Balsamo, Tiziana Venesio, Jessica Giordano, Daniela Conticelli, Tânia Capelôa, Marilisa Cargnelutti, Daniel Moya-Rull, Silvia Menegon, Laura D’Errico, Stefano Ughetto, Cristina Migliore, Stefania Durando, Maria Apicella, Sara E. Bellomo, Claudio Isella, and Simona Corso

Abstract

Baseline characteristics of the 349 enrolled patients.

Published
2023

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