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Caraglia 2009 ). Additional investigation is needed to validate the clinical relevance
of individual genetic differences.
In 2011, OncoTrack, an international consortium of academic researchers, phar-
maceutical companies, and commercial partners, launched a 5-year project to
develop and assess new biomarkers for CRC. Total budget for the project along with
funding from the Innovative Medicines Initiative – a private-public partnership
between the pharmaceutical industry and the European Union – amounts to €25.8
million ($35.6 million). OncoTrack was founded to create next-generation methods
of biomarker development to develop personalized treatment of CRC. The consor-
tium, led by Bayer HealthCare Pharmaceuticals and the Max Planck Institute for
Molecular Genetics in Germany, includes AstraZeneca, Boehringer Ingelheim,
Janssen Pharmaceutica, Merck, Pfi zer, and Roche Diagnostics. Academic partners
include Uppsala University, University College London, Paris South University,
Charité Universitätsmedizin Berlin, Medizinische Universität Graz, and Technische
Universität Dresden. International Prevention Research Institute, Experimental
Pharmacology and Oncology, and Alacris Theranostics also are members of
OncoTrack. The consortium’s fi rst project called “Methods for systematic next-
generation oncology biomarker development” will seek to generate high-quality
genomic and epigenetic data from clinically well-defi ned CRC tumors and their
metastases. The data will be compared to the germline genome of the patients, and
will be complemented by a detailed molecular characterization of the tumors.
OncoTrack will establish and characterize a new series of xenograft tumor models
and cell lines derived from the same set of tumors in order to support tumor biology
research and the early stages of biomarker qualifi cation. The combined data from all
phases of the project will enable OncoTrack to address fundamental questions
regarding the relationship between tumor genotype and phenotype, thus providing
the starting point for discovery and selection of suitable candidates for development
as biomarkers of CRC.
Sequencing for Personalized Management of Colorectal Cancer
The Cancer Genome Atlas project plans to profi le genomic changes in 20 different
cancer types and has now presented results from multidimensional analyses of
human CRC. The distinction between the colon and the rectum is largely anatomi-
cal, but it has both surgical and radiotherapeutic management implications as well
as an impact on prognosis. Most investigators divide CRC biologically into those
with microsatellite instability (MSI; located primarily in the right colon and fre-
quently associated with the CpG island methylator phenotype and hyper-mutation)
and those that are microsatellite stable but chromosomally unstable.
Previous investigations have uncovered several critical genes and pathways that
are important in the initiation and progression of CRC. These include the WNT,
RAS-MAPK, PI3K, TGF-β, P53 and DNA mismatch-repair pathways. Large-scale
sequencing analyses have identifi ed numerous recurrently mutated genes and a
recurrent chromosomal translocation, but a fully integrated view of the genetic and
10 Personalized Therapy of Cancer