Investigating Optimal Chemotherapy Options for Osteosarcoma Patients through a Mathematical Model

Cells. 2021 Aug 6;10(8):2009. doi: 10.3390/cells10082009.

Abstract

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-γ 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.

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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / immunology
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cisplatin / administration & dosage
  • Clinical Decision-Making*
  • Cytotoxicity, Immunologic / drug effects
  • Decision Support Techniques*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • HMGB1 Protein / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Methotrexate / administration & dosage
  • Models, Theoretical*
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / immunology
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Patient Selection
  • Precision Medicine
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Time Factors
  • Tumor Microenvironment

Substances

  • HMGB1 Protein
  • HMGB1 protein, human
  • IFNG protein, human
  • Doxorubicin
  • Interferon-gamma
  • Cisplatin
  • Methotrexate