4.6 Article

Investigating Optimal Chemotherapy Options for Osteosarcoma Patients through a Mathematical Model

Journal

CELLS
Volume 10, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/cells10082009

Keywords

osteosarcoma; data driven mathematical model; immune infiltrations; chemotherapy; precision medicine; optimal dosage; doxorubicin; cisplatin; methotrexate

Categories

Funding

  1. National Cancer Institute of the National Institutes of Health [R21CA242933]

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This study developed a mathematical model for osteosarcoma, analyzing three clusters of tumors with unique immune profiles to suggest optimal drug dosages. The effects of chemotherapy regimens and treatment start times on immune and cancer cell behaviors were investigated. The results showed that the MAP regimen was effective in killing cancer cells, and consideration of the tumor's growth rate is crucial when determining treatment details.
Since all tumors are unique, they may respond differently to the same treatments. Therefore, it is necessary to study their characteristics individually to find their best treatment options. We built a mathematical model for the interactions between the most common chemotherapy drugs and the osteosarcoma microenvironments of three clusters of tumors with unique immune profiles. We then investigated the effects of chemotherapy with different treatment regimens and various treatment start times on the behaviors of immune and cancer cells in each cluster. Saliently, we suggest the optimal drug dosages for the tumors in each cluster. The results show that abundances of dendritic cells and HMGB1 increase when drugs are given and decrease when drugs are absent. Populations of helper T cells, cytotoxic cells, and IFN-gamma grow, and populations of cancer cells and other immune cells shrink during treatment. According to the model, the MAP regimen does a good job at killing cancer, and is more effective than doxorubicin and cisplatin combined or methotrexate alone. The results also indicate that it is important to consider the tumor's unique growth rate when deciding the treatment details, as fast growing tumors need early treatment start times and high dosages.

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