%0 Journal Article
%T A Composite Synergistic Systems Model for Exploring the Efficacies of Different Chemotherapeutic Strategies in Cancer
%A Probir Kumar Dhar
%A Durjoy Majumder
%J Computational Biology Journal
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/301369
%X 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. 1. Introduction Generally cancer cells survive by the growth of microvasculature (MV) around it, a process called angiogenesis. In recent time, different drugs called antiangiogenic (AAG) drugs are developed for hampering these MV cellsĄŻ growth [1¨C5]. Conventionally chemotherapeutic drugs (CD) are applied to the cancer patients with Maximum Tolerable Dosing (MTD) strategy. MTD application has a damaging effect on the blood vasculature (BV) around the tumor, thereby limiting the availability of the CD to the tumor. Generally, a gap period is allowed between two consecutive MTD drug applications to nullify the damaging toxic effect of MTD to the physiological system. This also helps in the restoration of the damaged BV around the tumor, so drug availability to the tumor can be expected in the consecutive MTD application. To enhance such support, autologous hematopoietic stem cell (HSC) transplantation is under clinical trials for different cancers [6¨C13]. In metronomic chemotherapy (MCT), conventional CD can be applied in low, but dose-dense strategy (with frequent interval). Efficacy of MCT strategy is established in different experimental and few clinical observations [4, 14¨C16]. MTD strategy is applied to
%U http://www.hindawi.com/journals/cbj/2013/301369/