Mathematical Modeling of Non-Small-Cell Lung Cancer Biology through the Experimental Data on Cell Composition and Growth of Patient-Derived Organoids

Life (Basel). 2023 Nov 20;13(11):2228. doi: 10.3390/life13112228.

Abstract

Mathematical models of non-small-cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with "omics" approaches will improve our understanding of the nature of non-small-cell lung cancer. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

Keywords: adenocarcinoma; cancer cells; cancer-associated fibroblasts; cell composition; cytotoxic T-lymphocytes; flow cytometry; mathematical modeling; non-small-cell lung cancer; tumor-associated macrophages.