banda transcan 2 2016ul

Title: Early detection of relapses in stage III colon cancer patients by longitudinally following a personalized molecular signature from a a blood test: THRuST

Project Coordinator:
Alain THIERRY (France) INSERM, Institut de Recherche en Cancerologie, Montpellier

Project Partners:
Elen ELEZ (Spain) Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona
Federica DI NICOLANTONIO (Italy) IRCCS Istituto di Candiolo- Fondazione del Piemonte per l'Oncologia, Candiolo (TO)
Marc YCHOU (France) Institut of Cancerologie Regional de Montpellier, Montpellier
Ramon SALAZAR (Spain) Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona
Srdjan NOVAKOVIC (Slovenia) Institut of Oncology Ljubljana, Ljubljana

Project Abstract:
Background and rationale: Mortality of colon cancer (CC) is highly associated with tumor relapse and the metastatic disease (50-70%). Despite advanced treatment and recommended more intensive surveillance strategies, increase of the overall rate of curative resection in recurrent patients relies on early detection of relapses. Tumour progression is characterised by the acquisition of distinct somatic mutations associated with clonal expansion. Temporal and intra-tumoral heterogeneity represents a major issue negatively affects the clinical outcome for advanced cancer patients. 
Hypothesis: Malignant tumors shed cell free DNA (cfDNA) into the blood stream. Analyzing this new biological source may have important implications in a shift towards personalized medicine for diagnosing and/or monitoring malignancies. 
Aims: Proof of concept of longitudinally following up an individualized tumour molecular signature from cfDNA analysis in post-surgery stage III CC patients. 
Methods: This study is a prospective, multicentre and blinded study on stage III CC. A molecular signature of 3 point mutations will be defined for each CC patient based on Next-generation sequencing on selected genes from plasma analysis at time of stage III CC diagnosis. Individual signatures will be composed of known drivers (TP53, APC,…) and, also driver mutations of genes involved in the EGFR pathway (RAS/BRAF/EGFR/PIK3CA). Patient follow up would be performed by IntPlex method which enables simultaneous determination of five parameters: the total concentration of cfDNA, the presence of a point mutation, the mutant DNA concentration, the mutant allele fractions of cfDNA, and the cfDNA fragmentation index. This study beneficiates from the genetic coverage of NGS approach for selecting the molecular signature and from the use of this Intplex Q-PCR based method facilitating rapid and cost-effective longitudinal analysis and enabling determination of quantitative cfDNA parameters. Specific cfDNA methylation pattern will be as well follow post-surgery. Blood of CC patient blood (n=315) will be collected before and after surgery. Data will be compared with clinical observations under standard management care, and conventional imaging methods and biomarkers. The project has a primary objective: to evaluate the clinical feasibility of following tumor progression by dynamically detecting a molecular and personalized signature from a blood test; and secondary objectives: (i), to examine the respective performance of each qualitative and quantitative cfDNA parameters; and (ii), descriptive knowledge on the clonal evolution of driver mutations under standard care; and (iii), surveillance, and compare data with conventional biomarkers and imaging. 
Expected results and potential impact: Positive outcome of this proof of concept study would warrant larger studies to demonstrate clinical validation and utility of this approach. This dynamic follow up might help physicians to better and earlier adjust treatment and to improve surveillance of CC patients. 


(Project funded under JTC 2016)


Launch of the call: JTC 2021
The new TRANSCAN-3 project consortium is launching the first Joint Transnational Call for proposals, co-funded by the European Commission, on:
"Next generation cancer immunotherapy: targeting the tumour microenvironment"

International Networking Event (virtual)
on 22 April 2021 hrs 9:00 CET
will focus on the forthcoming co-funded JTC 2021 on:
"Next generation cancer immunotherapy: targeting the tumour microenvironment" 
the event is organized by TUBITAK under the “Turkey in Horizon 2020 Phase II” Technical Assistance Project
in cooperation with TRANSCAN-3

 Sustained collaboration of national and regional programmes in cancer research
is the new project funded by the European Commission under H2020  which started on 1st March 2021 and will last five years (G. A. no. 964264)

A TRANSCAN-2 brochure, highlighting key achievements, is available for download


eu flagship

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643638.

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