Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-oncology Research

Author:

Chambers Laura1ORCID,Haight Paulina1ORCID,Chalif Julia1ORCID,Mehra Yogita2ORCID,Spakowicz Daniel2ORCID,Backes Floor J.1ORCID,Cosgrove Casey M.1ORCID,O’Malley David M.1ORCID,Vargas Roberto3ORCID,Corr Bradley R.4ORCID,Bae-Jump Victoria L.5ORCID,Arend Rebecca C.6ORCID

Affiliation:

1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, James Hospital and Solove Research Institute, Columbus, Ohio. 1

2. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. 2

3. Division of Gynecologic Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio. 3

4. Division of Gynecologic Oncology, University of Colorado, Denver, Colorado. 4

5. Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina. 5

6. Department of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, Alabama. 6

Abstract

Abstract Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued preclinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for the evaluation of the tumor–immune interaction in an immunocompetent host, most closely mimicking the tumor–immune interaction in patients with cancer. Unfortunately, significant disparities exist about syngeneic models in gynecologic malignancy, in which queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Published data exist about the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for preclinical models in endometrial and cervical cancers will support physician scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.

Funder

Doris Duke Charitable Foundation

John Templeton Foundation

Publisher

American Association for Cancer Research (AACR)

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