High-performance biomechanical model of combined immunotherapy and anti-angiogenic cancer treatment

Descripción del proyecto

La vía vascular hacia una inmunoterapia eficaz

El crecimiento tumoral y la administración de tratamientos dependen en gran medida de la vascularización del propio tumor. Las células tumorales producen unas moléculas que fomentan la angiogénesis, la cual apoya su rápido crecimiento y la transición de tumores benignos a tumores malignos. Estas moléculas también hacen que los vasos sanguíneos sean permeables y porosos. Esta última característica ayuda a las células tumorales a entrar en el torrente sanguíneo y propagarse, a la vez que hacen peligrar la administración de quimioterapia e inmunoterapia. Un grupo de científicos financiado con fondos europeos está desarrollando modelos informáticos de microentornos tumorales y reparación de anomalías vasculares para comprender mejor los efectos de una perfusión vascular optimizada en inmunoterapias prometedoras. Las predicciones se probarán en modelos experimentales.

Objetivo

Inefficient delivery of cellular and molecular medicines to solid tumors can reduce dramatically the efficacy of treatment and affect negatively patient’s survival. This explains in large part why standard chemo- and immune-therapies often fail to treat specific cancer types, even though these therapies are potent enough to eradicate cancer cells. Abnormalities in the structure of the tumor vasculature hinder tumor perfusion and as a result the systemic delivery of the medicines. In many tumor types, blood vessels are hyper-permeable, leaving large interendothelial openings, which causes fluid loss from the vascular to the interstitial tumor space. Vessel hyper-permeability can reduce tumor blood flow, rendering tumors hypo-perfused and hypoxic. Impaired blood supply and hypoxia help cancer cells evade the immune system and increase their invasive and metastatic potential. Normalization of the tumor vasculature is a clinical strategy to repair vascular abnormalities in order to improve perfusion, oxygenation and delivery of medicines. Immunotherapy is gaining interest as an effective therapeutic approach against cancer, but only a subset of patients receiving immunotherapy exhibit sustained tumor shrinkage. Here, we hypothesize that vascular normalization can improve immunotherapy. The objective of the proposed research is the optimal design of the combined immunotherapy and vascular normalization therapeutic approach. To this end, a numerical and experimental study is proposed to model and experimentally validate the vascular normalization procedure, focusing on its combined effects with immunotherapeutic drugs. The proposed research/training will complement the Applicant’s skills in high-performance computing, advanced optimization algorithms and artificial neural networks with the Host’s expertise in tumor microenvironment and cancer drug delivery to enhance his professional maturity and promote international collaborations.