Speaker
Description
Understanding glioblastoma resistance and recurrence remains a primary challenge in oncology. PDE models remain critical tools in the study of their underlying biology \cite{A2019}. In this study, we model a glioblastoma cell population, analyzing the distribution of resistance levels across the population under various treatment levels. Specifically, we investigate the "convection factor," which represents the epigenetic capacity of cells to transition toward higher resistance states in response to different stress types. A core challenge involves the use of a non-differentiable profile, which significantly complicates the calculation; we successfully derive an analytical solution for the governing system of equations. Our improved model extends beyond resistance accumulation to analyze the reversibility of these effects; specifically, the biological mechanisms that drive cells from resistant-senescent states back to more vulnerable phenotypes. By parameterizing our model and fitting it to experimental data \cite{PicholThievend2024}, we quantify the significance of various resistance-inducing factors. Crucially, this framework allows us to estimate the time scales required for phenotypic reversion, providing a robust basis for optimizing radiation therapy schedules. Ultimately, our approach enables the exploration of diverse therapeutic strategies, offering precise insights into how we may manipulate cell states to maximize vulnerability and improve clinical efficacy.
Bibliography
@article{PicholThievend2024,
title = {VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance},
volume = {15},
ISSN = {2041-1723},
url = {http://dx.doi.org/10.1038/s41467-024-47985-z},
DOI = {10.1038/s41467-024-47985-z},
number = {1},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
author = {Pichol-Thievend, Cathy and Anezo, Oceane and Pettiwala, Aafrin M. and Bourmeau, Guillaume and Montagne, Remi and Lyne, Anne-Marie and Guichet, Pierre-Olivier and Deshors, Pauline and Ballestín, Alberto and Blanchard, Benjamin and Reveilles, Juliette and Ravi, Vidhya M. and Joseph, Kevin and Heiland, Dieter H. and Julien, Boris and Leboucher, Sophie and Besse, Laetitia and Legoix, Patricia and Dingli, Florent and Liva, Stephane and Loew, Damarys and Giani, Elisa and Ribecco, Valentino and Furumaya, Charita and Marcos-Kovandzic, Laura and Masliantsev, Konstantin and Daubon, Thomas and Wang, Lin and Diaz, Aaron A. and Schnell, Oliver and Beck, J\"{u}rgen and Servant, Nicolas and Karayan-Tapon, Lucie and Cavalli, Florence M. G. and Seano, Giorgio},
year = {2024},
month = apr
}
@article{A2019,
title = {Interplay of Darwinian Selection, Lamarckian Induction and Microvesicle Transfer on Drug Resistance in Cancer},
volume = {9},
ISSN = {2045-2322},
url = {http://dx.doi.org/10.1038/s41598-019-45863-z},
DOI = {10.1038/s41598-019-45863-z},
number = {1},
journal = {Scientific Reports},
publisher = {Springer Science and Business Media LLC},
author = {Álvarez-Arenas, Arturo and Podolski-Renic, Ana and Belmonte-Beitia, Juan and Pesic, Milica and Calvo, Gabriel F.},
year = {2019},
month = jun
}
