Computational systems biology approaches to anti-angiogenic cancer therapeutics

Abstract

Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. Anti-angiogenic therapy involves inhibiting multiple cell types, molecular targets, and intracellular signaling pathways. Computational tools are useful in guiding treatment strategies, predicting the response to treatment, and identifying new targets of interest. Here, we describe progress that has been made in applying mathematical modeling and bioinformatics approaches to study anti-angiogenic therapeutics in cancer.

Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network

“…In humans, system biology has been used for the study of drug discovering using models of intracellular signaling networks [27], identification of new therapeutic targets in prion disease [28], and to understand complex process such as autophagy [29]. One of the strategies to understand a cell metabolism from a system biology approach involves the use of genome-scale metabolic constraint-based reconstructions [30]; which are assembled in a bottom-up approach based on genome annotation, biochemical, and physiological data [31].…”

Parameters Involved in Autophosphorylation in Chronic Myeloid Leukemia: a Systems Biology Approach

“…These mathematical models were successfully implemented to analyze various interactions among components of the particular pathways and simulate them to the environmental factors or external signals (MarshallColon et al, 2014;Finley et al, 2014;Wu et al, 2014). On the other hand, it also enables to explore the system function at various levels and help to generate hypothesis about biological experiments.…”

The impact of tumor receptor heterogeneity on the response to anti-angiogenic cancer treatment

“…Various modeling approaches have been applied to study anti-angiogenesis therapies, including differential equation based models, Boolean network models, multicompartment models, hybrid cellular automaton models, multiscale agent-based models, image-based models and bioinformaticsbased modeling. 18 In particular, the effects of anti-VEGF agents on VEGF and its receptors have been intensively investigated with computational modeling. Targeting VEGF binding, VEGF secretion and VEGFR signaling as anti-angiogenic strategies have been illustrated in different studies.…”

“…Targeting VEGF binding, VEGF secretion and VEGFR signaling as anti-angiogenic strategies have been illustrated in different studies. 18 Recently, mathematical modeling was used to understand the impact of the cross-talk between tumor cells and endothelial cells 19 and the vascular phenotypes 20 on the effects of anti-angiogenic treatment, which generates new insights of anti-angiogenic therapy using mathematical modeling. Each model provides quantitative insight into the response to various anti-angiogenic strategies, at different levels of detail and scales, ranging from intracellular signaling to whole-body dynamics.…”