A Composite Synergistic Systems Model for Exploring the Efficacies of Different Chemotherapeutic Strategies in Cancer

Abstract

Different chemotherapeutic strategies like Maximum Tolerable Dosing (MTD), Metronomic Chemotherapy (MCT), and Antiangiogenic (AAG) drug are available; however, the selection of the best therapeutic strategy for an individual patient remains uncertain till now. Several analytical models are proposed for each of the chemotherapeutic strategies; however, no single analytical model is available which can make a comparative assessment regarding the long-term therapeutic efficacy among these strategies. This, in turn, may limit the clinical application of such analytical models. To address this issue here we developed a composite synergistic system (CSS) model. Through this CSS model, comparative assessment among the MTD, MCT, and AAG drug therapy can be assessed. Moreover, these chemotherapeutic strategies along with different supportive therapies like Hematopoietic Stem Cell transplantation (HSC), cellular immunotherapy as well as different combinations among these therapeutic strategies can be assessed. Fitting of initial clinical data of individual clinical cases to this analytical model followed by simulation runs may help in making such decision. Analytical assessments suggest that with the considered tumor condition MCT alone could be more effective one than any other therapeutics and/or their combinations for controlling the long-term tumor burden.

Efficacy and Toxicity Assessment of Different Antibody Based Antiangiogenic Drugs by Computational Docking Method

“…Though different analytical and simulation based studies showed that the efficacies of such drugs may have better in control of tumor growth, different clinical reports suggest that these monoclonal antibody based drugs do not qualify towards the expected criteria of overcoming the physiological toxicity [ 22 , 23 ]. This, in turn, may limit the wider acceptance of AAG drugs for cancer treatment.…”

Efficacy and Toxicity Assessment of Different Clinically Used Small Molecular Tyrosine Kinase Inhibitors by Computational Molecular Docking Method

“…Reports suggest that most of the small molecular tyrosine kinase inhibitors have an immunomodulatory role [10]. Perhaps the greatest advantage of sAAG drugs in future could be used for targeted therapies by inserting in liposomes [11] or can be applied through MCT (metronomic dosing strategy, where chemotherapeutic drugs are applied with dose-dense mode i.e., very low doses but with a frequent intervals) strategy; hence can be applied orally [12][13][14][15][16][17][18]. There are several sAAG drugs now available for clinical use and the list is growing in number; however, most of them have a molecular weight ranges from 130 to 600.…”