Can Differentiation Therapy Control Cancer-Stem-Cell Driven Tumors?

C.A. CONDAT; L. BENITEZ; L. BARBERIS; J. FOTINOS

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Congreso; SOLABIMA 2022 - Mini-simpósio:Modelagem matemática e computacional do câncer; 2022

Sociedad Latinoamericana de Biologia Matematica

Tumor growth is often driven by chemo- and radiotherapy-resistant cancer stem cells (CSCs). A possible therapeutic course consists in administering an agent that differentiates the CSCs while using conventional therapies to eliminate the differentiated cancer cells (DCCs). Here we formulate a two-population (CSCs and DCCs) model that describes the action of a differentiating agent. We analyze its mathematical properties, finding the system equilibria and their stability; we also build phase diagrams that describe the system evolution and the effects of the differentiation therapy. To obtain realistic predictions, we choose the model parameters to be those determined from fits to various experimental datasets. These datasets describe the progression of tumorspheres under different culture conditions. Typically, there is a range of values of the therapy efficiency such that the tumor’s final state has a CSC fraction, but a strong enough therapy leads to the suppression of this phenotype. We also find that different external conditions lead to remarkably diverse behaviors. In summary, our model shows how the effects of a differentiation therapy depend critically not only on the dosage and timing of the drug application but also on the tumor nature and its environment.