Investigating Optimal Chemotherapy Options for Osteosarcoma Patients through a Mathematical Model.

Trang Le,Sumeyye Su,Leili Shahriyari

doi:10.3390/cells10082009

Abstract

Simple SummaryOsteosarcoma is a rare type of cancer with poor prognoses. However, to the best of our knowledge, there are no mathematical models that study the impact of chemotherapy treatments on the osteosarcoma microenvironment. In this study, we developed a data driven mathematical model to analyze the dynamics of the important players in three groups of osteosarcoma tumors with distinct immune patterns in the presence of the most common chemotherapy drugs. The results indicate that the treatments’ start times and optimal dosages depend on the unique growth rate of the tumor, which implies the necessity of personalized medicine. Furthermore, the developed model can be extended by others to build models that can recommend individual-specific optimal dosages.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- 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.

Highlights

Osteosarcoma is a rare kind of cancer that occurs in the bone, and around 1000 new cases of osteosarcoma are identified each year in the United States [1]
The most common chemotherapy regimen for osteosarcoma in children and young adults is the MAP regimen, which is a combination of doxorubicin, cisplatin, and high-dose methotrexate [39]
We studied the dynamics of cell and cytokine populations in large osteosarcoma tumors during neoadjuvant MAP treatment, which includes two

Summary

Introduction

Osteosarcoma is a rare kind of cancer that occurs in the bone, and around 1000 new cases of osteosarcoma are identified each year in the United States [1]. It can affect people of any age, but it mostly occurs in children who are 10 to 14 and in adults who are 65 and older [2,3]. Improve survival rates, and achieve precision medicine, we need to investigate osteosarcoma tumor progression and identify the primary factors in the growth of tumors for each patient [12]

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