Evolution of tumor stress response during cytoreductive surgery for ovarian cancer
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.
Authors
- Taha Merghoub (ORCID: https://orcid.org/0000-0002-1518-5111)
- Ana Leda F. Longhini (ORCID: https://orcid.org/0000-0002-2817-725X)
- Melih Arda Ozsoy (ORCID: https://orcid.org/0009-0000-8234-0954)
- Aaron Praiss (ORCID: https://orcid.org/0000-0001-6045-6067)
- Dmitriy Zamarin (ORCID: https://orcid.org/0000-0002-0094-0161)
- Rui Gardner (ORCID: https://orcid.org/0000-0002-7270-5136)
- Melica Nourmoussavi Brodeur (ORCID: https://orcid.org/0000-0002-7595-0313)
- Ginger J. Gardner (ORCID: https://orcid.org/0000-0003-3955-3238)
- Giulio Pesci
- Fatemeh Derakhshan (ORCID: https://orcid.org/0000-0002-1346-589X)
- Britta Weigelt (ORCID: https://orcid.org/0000-0001-9927-1270)
- Tiffany Sia (ORCID: https://orcid.org/0000-0001-7890-207X)
- S. Dennis (ORCID: https://orcid.org/0000-0002-3105-8913)
- Timothy Hoang (ORCID: https://orcid.org/0000-0002-3012-3461)
- Oliver Zivanovic (ORCID: https://orcid.org/0000-0003-1305-4991)
- Kara Long Roche (ORCID: https://orcid.org/0000-0003-0342-2922)
- Yukio Sonoda
- Etta Hanlon
- Ryan Kahn (ORCID: https://orcid.org/0000-0002-5596-6238)
- Lea A. Moukarzel (ORCID: https://orcid.org/0000-0002-6987-6962)
- Yingjie Zhu (ORCID: https://orcid.org/0000-0003-1849-6019)
- Hunter Green (ORCID: https://orcid.org/0009-0002-3944-6803)
- Nadeem R. Abu-Rustum
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- Cornell University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- iScience
- Published
- 2025-03-31
- DOI
- https://doi.org/10.1016/j.isci.2025.112317
- Citations
- 1
- Primary Topic
- Ovarian cancer diagnosis and treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.70
Funders
- Breast Cancer Research Foundation
- Ovarian Cancer Research Fund Alliance
- Cycle for Survival
- National Institutes of Health
- National Cancer Institute