Project description
Noninvasive detection of senescence
Cellular senescence is a physiological process associated with cell growth arrest following damage and stress stimuli. Initially discovered in cells following serial cultivation, senescence halts the proliferation of premalignant cells and thus has important consequences for cancer. Also, senescence is a marker for cancer treatment outcomes, but its detection requires invasive biopsies. Funded by the European Research Council, the SenPET project proposes to develop a radiolabeled positron emission tomography (PET) tracer for detecting senescence. Following validation in various human and mouse models, researchers will test the senescence PET tracer in patients with gastrointestinal tumours. The study will offer a noninvasive imaging approach for monitoring response to therapy in patients with cancer.
Objective
The irreversible growth arrest, termed cellular senescence, plays a key role in tumor progression and promotion, as well as in many other physiological processes. It has been shown to be a predictive marker for the long term outcome of cancer treatment and novel therapies aiming at the elimination of senescent cells are under development (i.e. senolytics). Therefore, techniques for the detection of senescence are of utmost importance. However, in the current clinical setting this is only possible with histological staining after collection of invasive biopsies and a tool for non-invasive assessment and quantification of senescence is highly desirable towards improved patient care and personalized medicine.
Within our current ERC project ImageLink we have developed a stable and reproducible synthesis protocol for a novel radiolabeled PET-tracer targeting ß-galactosidase, the “gold-standard” biomarker of senescence. The tracer was validated in several in vitro and in vivo human and murine tumor models. A clear distinction between senescent and non-senescent tumors was possible and the convincing results have encouraged us to translate our preclinical findings into a clinical setting. However, this step exceeds the scope of our current ERC project.
Within the planned project SenPET we will establish an automated radiosynthesis of the tracer that is compliant with good manufacturing practice (GMP) and all necessary paperwork with the authorities for approval of a clinical study will be accomplished. Finally we will perform the first clinical proof of concept study of a senescence PET tracer in 10 patients suffering from gastrointestinal tumors. PET data with our novel tracer will be collected before and after a senescence inducing chemotherapy treatment and correlated with ex vivo markers of senescence. Since our tracer is protected by patent applications, the results of this study will help us to team up with industrial partners to perform larger clinical studies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesclinical medicineoncology
- medical and health scienceshealth sciencespersonalized medicine
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Topic(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
72074 Tuebingen
Germany