A living ex vivo platform for functional, personalized brain cancer diagnosis

Breanna Mann; Xiaopei Zhang; Noah Bell; Adebimpe Adefolaju; Morrent Thang; Rajaneekar Dasari; Krishna Kanchi; Alain Valdivia; Yang Yang; Andrew Buckley; Vivien Lettry; Carolyn Quinsey; Yasmeen Rauf; David Kram; Noah Cassidy; Cyrus Vaziri; David L Corcoran; Stephen Rego; Yuchao Jiang; Lee M Graves; Denise Dunn; Scott Floyd; Albert Baldwin; Shawn Hingtgen; Andrew B Satterlee

doi:10.1016/j.xcrm.2023.101042

A living ex vivo platform for functional, personalized brain cancer diagnosis

Cell Rep Med. 2023 Jun 20;4(6):101042. doi: 10.1016/j.xcrm.2023.101042. Epub 2023 May 15.

Authors

Breanna Mann¹, Xiaopei Zhang¹, Noah Bell¹, Adebimpe Adefolaju², Morrent Thang³, Rajaneekar Dasari², Krishna Kanchi⁴, Alain Valdivia¹, Yang Yang⁵, Andrew Buckley¹, Vivien Lettry¹, Carolyn Quinsey⁶, Yasmeen Rauf⁷, David Kram⁸, Noah Cassidy⁹, Cyrus Vaziri⁵, David L Corcoran⁴, Stephen Rego¹⁰, Yuchao Jiang¹¹, Lee M Graves¹², Denise Dunn¹³, Scott Floyd¹³, Albert Baldwin¹⁰, Shawn Hingtgen¹⁴, Andrew B Satterlee¹⁵

Affiliations

¹ Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Eshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Department of Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁶ Department of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ Department of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ Division of Pediatric Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁹ School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁰ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹¹ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹² Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹³ Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
¹⁴ Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: hingtgen@email.unc.edu.
¹⁵ Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: satterle@email.unc.edu.

Abstract

Functional precision medicine platforms are emerging as promising strategies to improve pre-clinical drug testing and guide clinical decisions. We have developed an organotypic brain slice culture (OBSC)-based platform and multi-parametric algorithm that enable rapid engraftment, treatment, and analysis of uncultured patient brain tumor tissue and patient-derived cell lines. The platform has supported engraftment of every patient tumor tested to this point: high- and low-grade adult and pediatric tumor tissue rapidly establishes on OBSCs among endogenous astrocytes and microglia while maintaining the tumor's original DNA profile. Our algorithm calculates dose-response relationships of both tumor kill and OBSC toxicity, generating summarized drug sensitivity scores on the basis of therapeutic window and allowing us to normalize response profiles across a panel of U.S. Food and Drug Administration (FDA)-approved and exploratory agents. Summarized patient tumor scores after OBSC treatment show positive associations to clinical outcomes, suggesting that the OBSC platform can provide rapid, accurate, functional testing to ultimately guide patient care.

Keywords: algorithm; brain cancer; brain slice; drug screening; ex vivo; functional precision medicine; patient tumor; pediatric; personalized therapies; translational.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Brain
Brain Neoplasms* / diagnosis
Brain Neoplasms* / genetics
Brain Neoplasms* / therapy
Child
Humans

Abstract

Publication types

MeSH terms

Grants and funding