FIGURE 1.

Generalized model of tumor cell response to multiple doses of doxorubicin treatment. We start with a population of untreated tumor cells and let them grow for approximately 48 h. At time $t_{Dox}^{\mathit{1}}$ , we add a dose of doxorubicin (Dox) to each well. We assume that after the treatment, the tumor cells either survive ( $S$ ) or are irreversibly damaged ( $D^{\mathit{1}}$ ) and ultimately die due to the cytotoxic action of doxorubicin. The fraction of cells in either subpopulation is determined by $f_s^{\mathit{1}}$ , the fraction of surviving cells after the first dose. After the subsequent $n_d$ doses of doxorubicin ( $i=\mathit{2,3},\dots ,n_d$ ), we assume that a fraction $f_s^i$ of the surviving cells survive the treatment, while a fraction ( $\mathit{1}-f_s^i$ ) induces a new subpopulation of irreversibly damaged cells ( $D^i)$ , such that the total number of tumor cells is $N=S+D^{\mathit{1}}+D^{\mathit{2}}+...{+D}^{n_d}$ for times $t>t_{Dox}^{n_d}$ . In this study, we further assess whether the collection of $f_s^i$ can be assumed to take on the same value or whether they require an independent parameterization with each doxorubicin dose. This Figure was created using BioRender.com.