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EPOCH28

Epigenetic Profiling of Chemotherapy Efficacy

Total Cost €

EC-Contrib. €

Partnership

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EPOCH28 project word cloud

Explore the words cloud of the EPOCH28 project. It provides you a very rough idea of what is the project "EPOCH28" about.

chromatin benefit predicts centromeres clinically docetaxel camptothecin landmarks signature drugs applicability efficacy underscored though cellular establishing breast variant commercial highlighted cenh3 28 26 trails mislocalization cancer predictive illustrate cells biomarkers cancers half gene maintaining received class irradiation team dna subjected companion xenograft individual samples patient off demonstrated predict gamma wish oncology context 31 gives thirdly proof centromeric models damage toxic link alone patients signatures derives spin expression clinical market histone vemurafenib discoveries regulators exists showcase notably overcome neoadjuvant sensitivity melanoma roche first secondly validating advantage adaptive preliminary discovery erc treatment lab diagnostics

Project "EPOCH28" data sheet

The following table provides information about the project.

Coordinator	INSTITUT CURIE Organization address address: rue d'Ulm 26 city: PARIS postcode: 75231 website: www.curie.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	France [FR]
Total cost	150˙000 €
EC max contribution	150˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2015-PoC
Funding Scheme	ERC-POC
Starting year	2015
Duration (year-month-day)	from 2015-11-01 to 2017-04-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	INSTITUT CURIE INSTITUT CURIE Organization address address: rue d'Ulm 26 city: PARIS postcode: 75231 website: www.curie.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS)	coordinator	150˙000.00

Map

Project objective

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.

Publications

List of publications.
year	authors and title	journal	last update
2016	Z. A. Gurard-Levin, L. O. W. Wilson, V. Pancaldi, S. Postel-Vinay, F. G. Sousa, C. Reyes, E. Marangoni, D. Gentien, A. Valencia, Y. Pommier, P. Cottu, G. Almouzni Chromatin Regulators as a Guide for Cancer Treatment Choice published pages: 1768-1777, ISSN: 1535-7163, DOI: 10.1158/1535-7163.MCT-15-1008	Molecular Cancer Therapeutics 15/7	2019-07-25

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The information about "EPOCH28" are provided by the European Opendata Portal: CORDIS opendata.