Preprint
A simple circuit to sustain intact tumor microenvironments for complex drug interrogations
bioRxiv
Cold Spring Harbor Laboratory, 1.2
10/28/2025
DOI: 10.1101/2025.10.26.684624
PMCID: PMC12636357
PMID: 41279433
Abstract
Deep learning and large language models can integrate complex datasets to uncover biological insights that are often undetectable through conventional analyses. With application to translational cancer research, these computational tools have positioned 3D patient-derived tumor avatars front and center as crucial data input sources. However, a major challenge remains: the lack of standardization in media composition in 3D patient-derived tumor models unpredictably affects cell behavior and limit the utility beyond predicting treatment responses. To address this unmet need, we developed a simple, reproducible perfusion circuit system to approximate in vivo physiology using autologous patient plasma. With peritoneal metastases and core needle biopsies across multiple tumor histologies, we demonstrate preservation of the tumor microenvironment for up to 48 hours using multi-modal interrogation techniques. With proof-of-concept experiments, we display the system’s ability to unveil complex drug-dependent biology within this time window. Standardizable, physiologically relevant platforms for 3D patient-derived tumor avatars will yield unprecedented insights through the integration of data from broad groups of patients and the use of an expanding armamentarium of artificial intelligence capabilities.
Details
- Title: Subtitle
- A simple circuit to sustain intact tumor microenvironments for complex drug interrogations
- Creators
- A Leila Sarvestani - National Institutes of HealthSamantha Ruff - National Institutes of HealthKirsten Remmert - National Institutes of HealthMartha Teke - National Institutes of HealthEmily Verbus - National Institutes of HealthAreeba Saif - National Institutes of HealthMarcial Garmendia-Cedillos - National Institute of Biomedical Imaging and BioengineeringAlex Rossi - National Institutes of HealthAshley Rainey - National Institutes of HealthKrystle Nomie - AddgeneSurajit Sinha - National Institutes of HealthMichael M. Wach - National Institutes of HealthCarrie Ryan - National Institutes of HealthStephanie N. Gregory - National Institutes of HealthPriyanka Desai - National Institutes of HealthAbir K. Panda - National Institute of Allergy and Infectious DiseasesEmily C. Smith - National Institutes of HealthReed Ayabe - National Institutes of HealthJames D. McDonald - National Institutes of HealthShreya Gupta - National Institutes of HealthTracey Pu - National Institutes of HealthTahsin Khan - National Institutes of HealthJacob Lambdin - National Institutes of HealthKenneth Luberice - National Institutes of HealthStephanie C. Lux - National Institutes of HealthHanna Hong - National Institutes of HealthImani Alexander - National Institutes of HealthSarfraz R. Akmal - National Institutes of HealthShahyan Rehman - National Institutes of HealthSophia Xiao - National Institutes of HealthJason Ho - National Institutes of HealthJustine Burke - National Institutes of HealthCathleen E. Hannah - National Cancer InstituteAlexandra Livanova - AddgeneAndrey Tyshevich - AddgeneStanislav Kurpe - AddgeneAndrey Kravets - AddgeneBasim Salem - AddgeneDaniil Vibe - BostonGene CorporationArina Tkachukv - AddgeneAnna Belozerova - AddgeneAleksandr Sarachakov - AddgeneEvgeny Barykin - AddgeneVladimir Kushnarev - AddgeneEkaterina Postovalova - AddgeneAlexander Bagaev - AddgeneNoemi Kedei - National Cancer InstituteMaria Hernandez - National Cancer InstituteBaktiar Karim - National Institutes of HealthDonna Butcher - National Institutes of HealthJennifer Matta - National Institutes of HealthMichael Kelly - National Cancer InstituteJatinder Singh - National Cancer InstituteTodd D. Prickett - National Institutes of HealthJames Hodge - National Institutes of HealthThorkell Andresson - Frederick National Laboratory for Cancer ResearchMichael B. Yaffe - Beth Israel Deaconess Medical CenterEthan M. Shevach - National Institute of Allergy and Infectious DiseasesDavid Kleiner - National Institutes of HealthJeremy L. Davis - National Cancer InstituteAndrew M. Blakely - National Institutes of HealthJonathan M. Hernandez - National Institutes of Health
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- Edition
- 1.2
- DOI
- 10.1101/2025.10.26.684624
- PMID
- 41279433
- PMCID
- PMC12636357
- NLM abbreviation
- bioRxiv
- ISSN
- 2692-8205
- eISSN
- 2692-8205
- Publisher
- Cold Spring Harbor Laboratory
- Number of pages
- 53
- Language
- English
- Date posted
- 10/28/2025
- Academic Unit
- Surgery
- Record Identifier
- 9985224315602771
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