Clinically oriented translational cancer multilevel modeling: The contracancrum project

Abstract

The ContraCancrum project aims at developing a composite multilevel platform for simulating malignant tumor development and tumor and normal tissue response to therapeutic modalities and treatment schedules. The project aims at having an impact primarily in (a) the better understanding of the natural phenomenon of cancer at different levels of biocomplexity and most importantly (b) the disease treatment optimization procedure in the patient's individualized context by simulating the response to various therapeutic regimens. Fundamental biological mechanisms involved in tumor development and tumor and normal tissue treatment response such as metabolism, cell cycle, tissue mechanics, cell survival following treatment etc. are modeled also addressing stem cells in the context of both tumor and normal tissue behavior. The simulators exploit several discrete and continuous mathematics methods such as cellular automata, the generic Monte Carlo technique, finite elements, differential equations, novel dedicated algorithms etc. The predictions of the simulators rely on the imaging, histopathological, molecular and clinical data of the patient. ContraCancrum deploys two important clinical studies for validating the models, one on lung cancer and one on gliomas. The crucial validation work is based on comparing the multi-level therapy simulation predictions with multi-level patient data, acquired before and after therapy. ContraCancrum aims to pave the way for translating clinically validated multilevel cancer models into clinical practice.