In Silico Oncology: Quantification of the In Vivo Antitumor Efficacy of Cisplatin-Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model
Fig 7
Scatterplots of the cell kill rate estimates vs. indicative model parameters and tumor proliferation features for the clinical cases 3 (Squamous Cell Carcinoma—SCC) and 12 (Adenocarcinoma—ADC).
All model parameters are varied simultaneously. The ordinate represents the sum of cisplatin and gemcitabine cell kill rates for case #3 (panels (A)-(I)) and cisplatin and vinorelbine cell kill rates for case #12 (panels (J)-(R)). The samples have a size of 146 and 175 for the SCC (#3) and ADC (#12) cases, respectively. They originate from two Latin Hypercube Sampling runs of 2000 combinations of parameter values after excluding the ones with negative cell proliferation kinetics or cell proliferation kinetics that fall beyond the reference values for non-small cell lung cancer in general and SCC and ADC representative cases specifically (see Results section). The scatterplots are displayed for the following model parameters and proliferation features: (A) and (J) duration of cell cycle, when considered equal for both stem and LIMP cells, (B) and (K) removal rate of DIFF cells defined as the number of cells that enter the apoptotic or necrotic pathway per hour, (C) and (L) fraction of stem cells that undergo symmetric division, (D) and (M) fraction of newborn cells that enter a quiescent state following mitosis, (E) and (N) fraction of cells that re-enter cell cycle from a quiescent state, when considered equal for both stem and LIMP cells, (F) and (O) number of mitoses performed by LIMP cells before becoming terminally differentiated, (G) and (P) resistance of stem cells to chemotherapy, expressed as the ratio of the stem cell kill rate to the estimated drug cell kill rate, (H) and (Q) the proportion of living tumor cells that are in a quiescent state, (I) and (R) the proportion of living tumor cells that are terminally differentiated. Abbreviations: ADC: Adenocarcinoma, SCC: Squamous cell carcinoma, LIMP: LImited Mitotic Potential tumor cell (also called committed or restricted progenitor cell), DIFF: terminally DIFFerentiated tumor cell. G0: dormant, resting phase.