Projektbeschreibung
Nanomechanische Biomarker für eine bessere personalisierte Krebstherapie
Tumoren sind stark heterogene Strukturen, die nicht nur zwischen Tumorarten, sondern auch innerhalb einer Art und je nach Progression der Erkrankung variieren. Wachsen solide Tumoren außerhalb des Wirtsgewebes, versteifen sie oftmals. Verursacht wird das durch die Zunahme an strukturellen Bestandteilen des Tumors selbst. Gleichzeitig drücken die mechanischen Kräfte innerhalb des Tumors die Blutgefäße zusammen, sodass Wirkstoffe nur schwer durchdringen. In jüngsten Studien hat sich gezeigt, dass eine Lockerungsstrategie mit antifibrotischen Mitteln zur Erweichung der Tumore beiträgt und die Wirkstoffzufuhr verbessert, was die Therapiemöglichkeiten erweitert. Das EU-finanzierte Projekt CancerFingerPrints wird mithilfe modernster Rasterkraftmikroskopie nanomechanische Biomarker entwickeln, mit denen sich die mechanischen Charakteristika der Tumoren quantifizieren lassen.
Ziel
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.
Wissenschaftliches Gebiet
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-POC - Proof of Concept GrantGastgebende Einrichtung
1678 Nicosia
Zypern