banda transcan 2 2016ul

Title: Mesalamine for Colorectal Cancer Prevention Program in Lynch syndrome.


Project Coordinator:
Christoph GASCHE (Austria) Medical University of Vienna, Vienna


Project Partners:
Judith KARNER-HANUSCH (Austria) Medical University of Vienna, Vienna
Jan LUBINSKI (Poland) Pomeranian Medical University, Szczecin
Gabriela MOSLEIN (Germany) HELIOS St. Josefs-Hospital Bochum-Linden, Bochum
Yaron NIV (Israel) Tel Aviv University, Rabin Medical Center, Tel Aviv
Hans F: VASEN (Netherlands) Leiden University Medical Center, Leiden


Project Abstract:
Patients with Lynch syndrome (LS), defined by having a hereditary mutation in at least one mismatch repair (MMR) gene, have a 50% lifetime risk for the development of colorectal cancer. The incidence of LS in Europe is estimated between 1 in 2000 to 1 in 370 individuals, a population of at least 250.000. Chemoprevention is a big hope for LS family members. Cancer development in LS occurs through a mutational mechanism called microsatellite instability (MSI). The genetic loss of MMR activity induces a mutator phenotype in which genetic deletions occur frequently in repetitive DNA sequences. In vitro, mesalamine (5-ASA), a well-tolerated drug that had been used for over 30 years in ulcerative colitis, reduces MSI via improvement of replication fidelity. In ulcerative colitis it seems to reduce the risk of colorectal cancer. In a genetic mouse model of LS 5-ASA reduced the tumor incidence, tumor multiplicity, and MSI. Here, we propose a multicenter, multinational, randomized, 3-arm, double blind, phase 2, clinical trial with 2400mg 5-ASA, 1200mg 5-ASA or placebo in LS patients for 2 years. Second, we intent to test for synergistic effects of 5-ASA and selected natural compounds (which also reduce MSI in vitro) in a mouse model of LS. Last, we intend to study the molecular effects of 5-ASA on activation of Nrf2, a protein that is involved in cellular stress response and that is activated by 18 out of 20 compounds, which all reduce MSI.

 

(Project funded under JTC 2012)


TRANSCAN News

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

ERA-NET Cofund 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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