Virtual clinical trials of BMP4-induced differentiation therapy identify strategies for combination with radiation therapy for glioblastoma patients

Society of Mathematical Biology MathEpiOnco joint meeting
MathOnco
GBM
Cancer Stem Cell
Virtual Clinical Trial
BMP4
Glioma Stem Cells
SMB
Authors
Affiliations

Nicholas Harbour

Center for Mathematical Medicine and Biology, University of Nottingham, UK

Lee Curtin

Mathematical Neuro-Oncology Lab, Mayo Clinci, AZ, USA

Matthew Hubbard

School of Mathematical Sciences, University of Nottingham, UK

Kristin Swanson

Mathematical Neuro-Oncology Lab, Mayo Clinci, AZ, USA

Markus Owen

Center for Mathematical Medicine and Biology, University of Nottingham, UK

Published

February 18, 2024

Abstract

GBM is the most aggressive and most common primary brain tumour in adults and is uniformly fatal, with a poor median survival time of 15 months. Standard of care for GBM consist of surgical resection followed by radio and chemotherapy, despite this resistance to treatment almost always occurs making recurrence inevitable. Failure of the current standard of care has been partly attributed to a special sub-population, the glioma stem cells (GSCs), which initiate and drive tumour growth. Treatment can not be successful unless all GSCs are eliminated. However, GSCs are known to be highly resistant to radiotherapy. New treatments that specifically target GSCs could have a potentially large benefit. BMP4 is known to induce differentiation of GSCs towards a less malignant, astrocytic-like lineage. Furthermore, new delivery systems (non-virally engineered adipose mesenchymal cells) provide a potential mechanism by which BMP4 could be successfully administered to reverse the GSC state and increase radio-sensitivity in patients. We develop a data-driven mechanistic mathematical model to create digital twins from patient data on which we perform in silico clinical trials to identify patient specific optimised treatment strategies.

Slides

Citation

BibTeX citation:
@misc{harbour2024,
  author = {Harbour, Nicholas and Curtin, Lee and Hubbard, Matthew and
    Swanson, Kristin and Owen, Markus},
  title = {Virtual Clinical Trials of {BMP4-induced} Differentiation
    Therapy Identify Strategies for Combination with Radiation Therapy
    for Glioblastoma Patients},
  date = {2024-02-18},
  langid = {en}
}
For attribution, please cite this work as:
Harbour, Nicholas, Lee Curtin, Matthew Hubbard, Kristin Swanson, and Markus Owen. 2024. “Virtual Clinical Trials of BMP4-Induced Differentiation Therapy Identify Strategies for Combination with Radiation Therapy for Glioblastoma Patients.”