Cel The aim of this proposal is to showcase that chromatin regulators represent a novel class of biomarkers that can predict the response to individual drugs. The proof of concept will be established by validating our recent discovery of a 28-gene signature of chromatin regulators that predicts the response of 26 out of 31 patient-derived xenograft breast cancer models to docetaxel. Notably, in patients treated with docetaxel, though all are subjected to toxic side effects, less than half of them clinically benefit, and no test exists to predict response. In the context of our funded ERC project, discoveries in our team underscored the key role of several chromatin regulators in establishing and maintaining chromatin landmarks, such as centromeres. In particular, our recent work demonstrated that mislocalization of the centromeric histone variant CenH3 gives cells an adaptive advantage to overcome DNA damage induced by camptothecin treatment and gamma irradiation. Further, preliminary evidence from our lab and others has highlighted a link between the expression level of chromatin regulators, including those involved in centromeres, and docetaxel sensitivity in a cellular context. Based on these promising studies, there are three aspects that we wish to develop as proof of concept for the use of chromatin regulators as novel predictive biomarkers for docetaxel treatment. First, we wish to further illustrate our chromatin regulators as a predictive signature for docetaxel treatment. For this, we will test samples from patients having received neoadjuvant docetaxel treatment alone. Secondly, we will test the applicability of our method in other cancers and drugs through an established collaboration with Roche to predict vemurafenib efficacy in melanoma. Thirdly, we will further evaluate the market need for predictive signatures for other commercial oncology drugs, and a potential spin-off that derives companion diagnostics for new drugs in clinical trails. Dziedzina nauki natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologyskin cancermelanomamedical and health sciencesclinical medicineoncologybreast cancer Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-PoC-2015 - ERC Proof of Concept Grant Zaproszenie do składania wniosków ERC-2015-PoC Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-POC - Proof of Concept Grant Instytucja przyjmująca INSTITUT CURIE Wkład UE netto € 150 000,00 Adres RUE D ULM 26 75231 Paris Francja Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 150 000,00 Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko INSTITUT CURIE Francja Wkład UE netto € 150 000,00 Adres RUE D ULM 26 75231 Paris Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 150 000,00