KMT2D Links TGF-β Signalling to Non-Canonical Activin Pathway and Regulates Pancreatic Cancer Cell Plasticity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE199856 | GEO | 2023/03/31
REPOSITORIES: GEO
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Project description:The paper describes a model on the size of pancreatic tumour.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Modeling Pancreatic Cancer Dynamics with Immunotherapy
Xiaochuan Hu, Guoyi Ke and Sophia R.-J. Jang
Bulletin of Mathematical Biology (2019) 81:1885–1915
Abstract:
We develop a mathematical model of pancreatic cancer that includes pancreatic cancer cells, pancreatic stellate cells, effector cells and tumor-promoting and tumor- suppressing cytokines to investigate the effects of immunotherapies on patient survival. The model is first validated using the survival data of two clinical trials. Local sen- sitivity analysis of the parameters indicates there exists a critical activation rate of pro-tumor cytokines beyond which the cancer can be eradicated if four adoptive trans- fers of immune cells are applied. Optimal control theory is explored as a potential tool for searching the best adoptive cellular immunotherapies. Combined immunother- apies between adoptive ex vivo expanded immune cells and TGF-β inhibition by siRNA treatments are investigated. This study concludes that mono-immunotherapy is unlikely to control the pancreatic cancer and combined immunotherapies between anti-TGF-β and adoptive transfers of immune cells can prolong patient survival. We show through numerical explorations that how these two types of immunotherapies are scheduled is important to survival. Applying TGF-β inhibition first followed by adoptive immune cell transfers can yield better survival outcomes.
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2024-09-02 | BIOMD0000000744 | BioModels