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Corso S, Pietrantonio F, Apicella M, et al. Optimized EGFR Blockade Strategies in . Clin Cancer Res. 2021;27(11):3126-3140doi: 10.1158/1078-0432.CCR-20-0121.
Corso, S., Pietrantonio, F., Apicella, M., Migliore, C., Conticelli, D., Petrelli, A., D'Errico, L., Durando, S., Moya-Rull, D., Bellomo, S. E., Ughetto, S., Degiuli, M., Reddavid, R., Fumagalli, U., De Pascale, S., Sgroi, G., Rausa, E., Baiocchi, G. L., Molfino, S., De Manzoni, G., Bencivenga, M., Siena, S., Sartore-Bianchi, A., Morano, F., Corallo, S., Prisciandaro, M., Di Bartolomeo, M., Gloghini, A., Marsoni, S., Sottile, A., Sapino, A., Marchiò, C., Dahle-Smith, A., Miedzybrodzka, Z., Lee, J., Ali, S. M., Ross, J. S., Alexander, B. M., Miller, V. A., Petty, R., Schrock, A. B., & Giordano, S. (2021). Optimized EGFR Blockade Strategies in . Clinical cancer research : an official journal of the American Association for Cancer Research, 27(11), 3126-3140. https://doi.org/10.1158/1078-0432.CCR-20-0121
Corso, Simona, et al. "Optimized EGFR Blockade Strategies in ." Clinical cancer research : an official journal of the American Association for Cancer Research vol. 27,11 (2021): 3126-3140. doi: https://doi.org/10.1158/1078-0432.CCR-20-0121
Corso S, Pietrantonio F, Apicella M, Migliore C, Conticelli D, Petrelli A, D'Errico L, Durando S, Moya-Rull D, Bellomo SE, Ughetto S, Degiuli M, Reddavid R, Fumagalli U, De Pascale S, Sgroi G, Rausa E, Baiocchi GL, Molfino S, De Manzoni G, Bencivenga M, Siena S, Sartore-Bianchi A, Morano F, Corallo S, Prisciandaro M, Di Bartolomeo M, Gloghini A, Marsoni S, Sottile A, Sapino A, Marchiò C, Dahle-Smith A, Miedzybrodzka Z, Lee J, Ali SM, Ross JS, Alexander BM, Miller VA, Petty R, Schrock AB, Giordano S. Optimized EGFR Blockade Strategies in . Clin Cancer Res. 2021 Jun 01;27(11):3126-3140. doi: 10.1158/1078-0432.CCR-20-0121. Epub 2021 Feb 04. PMID: 33542076.
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Clin Cancer Res. 2021 Jun 01;27(11):3126-3140. doi: 10.1158/1078-0432.CCR-20-0121. Epub 2021 Feb 04.

Optimized EGFR Blockade Strategies in .

Clinical cancer research : an official journal of the American Association for Cancer Research

Simona Corso, Filippo Pietrantonio, Maria Apicella, Cristina Migliore, Daniela Conticelli, Annalisa Petrelli, Laura D'Errico, Stefania Durando, Daniel Moya-Rull, Sara E Bellomo, Stefano Ughetto, Maurizio Degiuli, Rossella Reddavid, Uberto Fumagalli, Stefano De Pascale, Giovanni Sgroi, Emanuele Rausa, Gian Luca Baiocchi, Sarah Molfino, Giovanni De Manzoni, Maria Bencivenga, Salvatore Siena, Andrea Sartore-Bianchi, Federica Morano, Salvatore Corallo, Michele Prisciandaro, Maria Di Bartolomeo, Annunziata Gloghini, Silvia Marsoni, Antonino Sottile, Anna Sapino, Caterina Marchiò, Asa Dahle-Smith, Zosia Miedzybrodzka, Jessica Lee, Siraj M Ali, Jeffrey S Ross, Brian M Alexander, Vincent A Miller, Russell Petty, Alexa B Schrock, Silvia Giordano

Affiliations

  1. Department of Oncology, University of Torino, Candiolo, Torino, Italy. [email protected] [email protected].
  2. Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.
  3. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  4. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
  5. Department of Oncology, University of Torino, Candiolo, Torino, Italy.
  6. Department of Oncology, University of Torino, Orbassano, Torino, Italy.
  7. Chirurgia Generale 2, Brescia, Italy.
  8. Surgical Oncology Unit, Department of Surgical Science, ASST Bergamo Ovest, Treviglio, Bergamo, Italy.
  9. Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy.
  10. Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Section of Surgery, University of Verona, Verona, Italy.
  11. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  12. Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  13. Department of Medical Sciences, University of Torino, Torino, Italy.
  14. Tayside Cancer Centre, Ninewells Hospital, Dundee, Scotland, United Kingdom.
  15. University of Aberdeen, Aberdeen, Scotland, United Kingdom.
  16. Foundation Medicine, Inc., Cambridge, Massachusetts.
  17. Department of Pathology, Upstate Medical University, Syracuse, New York.
  18. Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom.

PMID: 33542076 DOI: 10.1158/1078-0432.CCR-20-0121

Abstract

PURPOSE: Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents.

EXPERIMENTAL DESIGN: We performed analyses on four cohorts: IRCC (570 patients), Foundation Medicine, Inc. (9,397 patients), COG (214 patients), and the Fondazione IRCCS Istituto Nazionale dei Tumori (206 patients). Preclinical trials were conducted in patient-derived xenografts (PDX).

RESULTS: The analysis of different gastroesophageal adenocarcinoma patient cohorts suggests that

CONCLUSIONS: This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a mAb as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors.

©2021 American Association for Cancer Research.

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