Description du projet
Le chemin vasculaire vers une immunothérapie efficace
La croissance tumorale et l’administration du traitement dépendent fortement de la vascularisation de la tumeur elle-même. Les cellules tumorales produisent des molécules qui favorisent l’angiogenèse, en soutenant leur croissance rapide et leur transition de tumeurs bénignes en tumeurs malignes. Ces molécules rendent également les vaisseaux sanguins coulants et poreux. Ces derniers aident les cellules tumorales à pénétrer dans le sang et à se propager tout en compromettant simultanément l’administration de chimiothérapies et d’immunothérapies. Des scientifiques financés par l’UE développent des modèles informatiques de microenvironnements tumoraux et de réparation d’anomalies vasculaires afin de mieux comprendre les effets d’une perfusion vasculaire optimisée sur des immunothérapies prometteuses. Les prévisions seront testées sur des modèles expérimentaux.
Objectif
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.
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MSCA-IF-EF-ST - Standard EFCoordinateur
1678 Nicosia
Chypre