A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery

DoctorEye: A clinically driven multifunctional platform, for accurate processing of tumors in medical images

Copyright @ Skounakis et al.This paper presents a novel, open access interactive platform for 3D medical image analysis, simulation and visualization, focusing in oncology images. The platform was developed through constant interaction and feedback from expert clinicians integrating a thorough analysis of their requirements while having an ultimate goal of assisting in accurately delineating tumors. It allows clinicians not only to work with a large number of 3D tomographic datasets but also to efficiently annotate multiple regions of interest in the same session. Manual and semi-automatic segmentation techniques combined with integrated correction tools assist in the quick and refined delineation of tumors while different users can add different components related to oncology such as tumor growth and simulation algorithms for improving therapy planning. The platform has been tested by different users and over large number of heterogeneous tomographic datasets to ensure stability, usability, extensibility and robustness with promising results. AVAILABILITY: THE PLATFORM, A MANUAL AND TUTORIAL VIDEOS ARE AVAILABLE AT: http://biomodeling.ics.forth.gr. It is free to use under the GNU General Public License

Object-Oriented Paradigms for Modelling Vascular\ud Tumour Growth: a Case Study

Motivated by a family of related hybrid multiscale models, we have built an object-oriented framework for developing and implementing multiscale models of vascular tumour growth. The models are implemented in our framework as a case study to highlight how object-oriented programming techniques and good object-oriented design may be used effectively to develop hybrid multiscale models of vascular tumour growth. The intention is that this paper will serve as a useful reference for researchers modelling complex biological systems and that these researchers will employ some of the techniques presented herein in their own projects

Advancement, applications, and future directions of 3D models in breast cancer research: a comprehensive review

3D models have popped up as indispensable tools for breast cancer study, they provide a closersemblance of the multiplex cellular and cancer tissue microenvironment as compared toancient 2D cultures. Their utilization in BC research permits a better interpretation ofhemostasis, cell-to-cell, and cell-to-extracellular matrix interactions, differentiation of cells,and tissue organization. 3D models qualify the exploration of numerous aspects regardingcancer progression, it also includes invasion of the tumor, cancer metastasis, and drugresistance, in a way that more precisely contemplates in vivo conditions. Hence, they provideda precise environment for research as compared to a complex in vivo host cell environment.This review highlights the importance of different 3D models in BC research, focusing on theircapability to enumerate complex disease physio-pathological features. This review explainsthe variety of 3D models utilized in BC research, encompassing Multicellular TumorSpheroids (MCTS), Three-Dimensional (3D) bioprinting, Organoid Models, Microfluidictechnologies, Organ on chip models, 3D hydrogel models and in silico approaches for BC,challenges and future of 3D models