Description du projet
Des biomarqueurs nanomécaniques pour un meilleur traitement personnalisé du cancer
Les tumeurs sont des structures très hétérogènes, avec des variations non seulement entre les types de tumeurs mais aussi entre les tumeurs d’un même type et en fonction de leur évolution. De nombreuses tumeurs solides se rigidifient au fur et à mesure de leur croissance dans les tissus de l’hôte. La rigidification est due à l’augmentation des composants structurels de la tumeur, et les forces mécaniques générées en son sein compriment les vaisseaux sanguins intratumoraux, ce qui diminue l’efficacité de l’administration de médicaments. Des études récentes ont démontré qu’une stratégie d’atténuation des contraintes, utilisant des agents antifibrotiques, favorise le ramollissement de la tumeur et facilite l’administration de médicaments, améliorant de ce fait la thérapie. Le projet CancerFingerPrints, financé par l’UE, utilisera la microscopie à force atomique de pointe pour développer des biomarqueurs nanomécaniques permettant de quantifier les caractéristiques mécaniques des tumeurs.
Objectif
In the fight against cancer, it is well recognized that tumors are highly heterogeneous and they might differ considerably not only between tumors types but also among tumors of the same type or even for the same tumor during progression. As a result, the efficacy of standard cancer chemotherapies varies, and while some patients respond to a particular treatment, other patients do not gain any benefit and in many cases, the condition of the patient deteriorates due to adverse effects. Consequently, crucial in cancer therapy is the prediction of a patient’s response to treatment. Failure of standard therapies has led to the introduction of a new era of personalized, patient-specific treatments, which are based on the identification of biomarkers that characterize the state of a particular tumor. Many solid tumors (e.g. breast cancers and sarcomas) stiffen as they grow in a host’s normal tissue. Stiffening is caused by an increase in the structural components of the tumor. As tumor tissue becomes stiffer, mechanical forces are generated within the tumor, that cause the compression of intratumoral blood vessels, resulting in compromised vessel functionality, which leads to poor drug delivery and therapeutic outcomes. Recently, it has been demonstrated that “stress-alleviation” strategy, which uses anti-fibrotic agents to promote tumor softening, improves uniform delivery of drugs and enhances therapy. Here, we propose the use of state-of-the-art Atomic Force Microscopy-AFM techniques for the development of a NanoMechanical biomarker, which will quantify the mechanical FingerPrints of Cancer. This biomarker will aim to: (i)predict the patient’s response to treatment with chemotherapy and (ii)monitor treatment outcomes, in the case of strategies that target tumor mechanical properties (e.g. stress-alleviation therapy). Furthermore, we propose to develop an AFM-based software product to be used as a commercial tool for the measurement of the NanoMechanical biomarker.
Champ scientifique
Programme(s)
Régime de financement
ERC-POC - Proof of Concept GrantInstitution d’accueil
1678 Nicosia
Chypre