Evolution of tumor stress response during cytoreductive surgery for ovarian cancer

Summary: Upfront treatment for patients with advanced high-grade serous ovarian cancer (HGSOC) includes a multi-hour cytoreductive surgery. Although the procedure is necessary for maximal tumor cytoreduction, understanding of the biology of systemic and intratumoral responses induced by surgical cyt...

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Main Authors: Aaron M. Praiss, Lea A. Moukarzel, Yingjie Zhu, Ana Leda F. Longhini, Fatemeh Derakhshan, Timothy Hoang, Giulio Pesci, Hunter Green, Melih A. Ozsoy, Etta Hanlon, Ryan Kahn, Melica Nourmoussavi Brodeur, Tiffany Sia, Nadeem R. Abu-Rustum, Ginger Gardner, Kara Long Roche, Yukio Sonoda, Oliver Zivanovic, Dennis S. Chi, Taha Merghoub, Rui Gardner, Britta Weigelt, Dmitriy Zamarin
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225005784
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author Aaron M. Praiss
Lea A. Moukarzel
Yingjie Zhu
Ana Leda F. Longhini
Fatemeh Derakhshan
Timothy Hoang
Giulio Pesci
Hunter Green
Melih A. Ozsoy
Etta Hanlon
Ryan Kahn
Melica Nourmoussavi Brodeur
Tiffany Sia
Nadeem R. Abu-Rustum
Ginger Gardner
Kara Long Roche
Yukio Sonoda
Oliver Zivanovic
Dennis S. Chi
Taha Merghoub
Rui Gardner
Britta Weigelt
Dmitriy Zamarin
author_facet Aaron M. Praiss
Lea A. Moukarzel
Yingjie Zhu
Ana Leda F. Longhini
Fatemeh Derakhshan
Timothy Hoang
Giulio Pesci
Hunter Green
Melih A. Ozsoy
Etta Hanlon
Ryan Kahn
Melica Nourmoussavi Brodeur
Tiffany Sia
Nadeem R. Abu-Rustum
Ginger Gardner
Kara Long Roche
Yukio Sonoda
Oliver Zivanovic
Dennis S. Chi
Taha Merghoub
Rui Gardner
Britta Weigelt
Dmitriy Zamarin
author_sort Aaron M. Praiss
collection DOAJ
description Summary: Upfront treatment for patients with advanced high-grade serous ovarian cancer (HGSOC) includes a multi-hour cytoreductive surgery. Although the procedure is necessary for maximal tumor cytoreduction, understanding of the biology of systemic and intratumoral responses induced by surgical cytoreduction is limited. Through analysis of matched tumor and normal tissues and peripheral blood collected at multiple time points during cytoreductive surgery in patients with HGSOC, we demonstrate that surgery leads to rapid induction of systemic inflammatory response and activation of inflammatory signaling in the tumor and normal tissue, with interleukin-6 emerging as a dominant inflammatory pathway. A parallel study in a syngeneic murine HGSOC model recapitulated these findings and demonstrated accelerated tumor growth in response to surgery. This study highlights the previously unappreciated impact of specimen collection timing on the tumor signaling networks and provides insights into stress pathways activated by surgery, generating rationale for perioperative therapeutic interventions to reduce protumorigenic effects.
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spelling doaj-art-61a0d5ac350c4dfeb672ffeb2c9d55e22025-08-20T02:16:29ZengElsevieriScience2589-00422025-05-0128511231710.1016/j.isci.2025.112317Evolution of tumor stress response during cytoreductive surgery for ovarian cancerAaron M. Praiss0Lea A. Moukarzel1Yingjie Zhu2Ana Leda F. Longhini3Fatemeh Derakhshan4Timothy Hoang5Giulio Pesci6Hunter Green7Melih A. Ozsoy8Etta Hanlon9Ryan Kahn10Melica Nourmoussavi Brodeur11Tiffany Sia12Nadeem R. Abu-Rustum13Ginger Gardner14Kara Long Roche15Yukio Sonoda16Oliver Zivanovic17Dennis S. Chi18Taha Merghoub19Rui Gardner20Britta Weigelt21Dmitriy Zamarin22Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Flow Cytometry, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USALudwig Collaborative Laboratory, Weill Cornell Medicine, New York, NY, USADepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of OB/GYN, Weill Cornell Medical College, New York, NY, USADepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of OB/GYN, Weill Cornell Medical College, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of OB/GYN, Weill Cornell Medical College, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of OB/GYN, Weill Cornell Medical College, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of OB/GYN, Weill Cornell Medical College, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of OB/GYN, Weill Cornell Medical College, New York, NY, USALudwig Collaborative Laboratory, Weill Cornell Medicine, New York, NY, USADepartment of Flow Cytometry, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USAPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding authorSummary: Upfront treatment for patients with advanced high-grade serous ovarian cancer (HGSOC) includes a multi-hour cytoreductive surgery. Although the procedure is necessary for maximal tumor cytoreduction, understanding of the biology of systemic and intratumoral responses induced by surgical cytoreduction is limited. Through analysis of matched tumor and normal tissues and peripheral blood collected at multiple time points during cytoreductive surgery in patients with HGSOC, we demonstrate that surgery leads to rapid induction of systemic inflammatory response and activation of inflammatory signaling in the tumor and normal tissue, with interleukin-6 emerging as a dominant inflammatory pathway. A parallel study in a syngeneic murine HGSOC model recapitulated these findings and demonstrated accelerated tumor growth in response to surgery. This study highlights the previously unappreciated impact of specimen collection timing on the tumor signaling networks and provides insights into stress pathways activated by surgery, generating rationale for perioperative therapeutic interventions to reduce protumorigenic effects.http://www.sciencedirect.com/science/article/pii/S2589004225005784Cell biologyCancer
spellingShingle Aaron M. Praiss
Lea A. Moukarzel
Yingjie Zhu
Ana Leda F. Longhini
Fatemeh Derakhshan
Timothy Hoang
Giulio Pesci
Hunter Green
Melih A. Ozsoy
Etta Hanlon
Ryan Kahn
Melica Nourmoussavi Brodeur
Tiffany Sia
Nadeem R. Abu-Rustum
Ginger Gardner
Kara Long Roche
Yukio Sonoda
Oliver Zivanovic
Dennis S. Chi
Taha Merghoub
Rui Gardner
Britta Weigelt
Dmitriy Zamarin
Evolution of tumor stress response during cytoreductive surgery for ovarian cancer
iScience
Cell biology
Cancer
title Evolution of tumor stress response during cytoreductive surgery for ovarian cancer
title_full Evolution of tumor stress response during cytoreductive surgery for ovarian cancer
title_fullStr Evolution of tumor stress response during cytoreductive surgery for ovarian cancer
title_full_unstemmed Evolution of tumor stress response during cytoreductive surgery for ovarian cancer
title_short Evolution of tumor stress response during cytoreductive surgery for ovarian cancer
title_sort evolution of tumor stress response during cytoreductive surgery for ovarian cancer
topic Cell biology
Cancer
url http://www.sciencedirect.com/science/article/pii/S2589004225005784
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