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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Personalized Cancer Medicine

Awarded: NOK 35.7 mill.

Project Manager:

Project Number:

218241

Application Type:

Project Period:

2012 - 2019

Location:

The Norwegian Cancer Genomics Consortium (NCGC) was founded by a group of dedicated oncologists, genome biologists and bioinformaticians across Norway, and is now extended to include university hospitals and universities in all health regions, the Norwegian Cancer Registry, the Biotechnology Advisory Board and Oslo Cancer Cluster. The consortium has acquired two large grants of totally 75 Mkr from the Norwegian research Council to develop a "National research and innovation platform for personalized cancer medicine". The consortium is collaborating with the Cancer Society, as a representative of the patients, the bioinformatics company PubGene, and the biotech-based pharma company BerGenBio. The Clinical trial units at Haukeland and Oslo University Hospitals are also involved. The NCGC has established infrastructure and competence for large-scale analysis of tumour genome data, and has currently on-going or planned research projects where tumour mutation profiles are determined for carefully selected cohorts from nine cancer types, melanoma, colorectal, lymphoma, multiple myeloma, sarcoma, leukemia, ovarian and prostate cancer. For the major cancer types various international studies have counted mutations already, but the quality of our clinical annotation and better selected and followed up patients give us an advantage. We focus on studies that can provide answers to important biological or clinical questions by selecting case groups, e.g. responders vs. nonresponders, time series, well-defined subtypes etc, or prospective, population-based cohorts for sarcomas, which have not yet been systematically profiled internationally. We also have a work package on preclinical validation of targets in models of the various cancer types, to validate known target mutations in new tissue contexts, or new mutations in known targets, and their therapeutic potential. We participate in the international cancer genomics benchmarking study as partners of the International Cancer Genomics Consortium (ICGC.org), to enable comparison and optimisation of bioinformatic analysis pipelines. Our Bioinformatics Team, headed by Prof. Eivind Hovig, participates as one of 15 international teams to ensure our methods are state-of-the-art. We also work with the cancer pathologists to establish streamlined diagnostic procedures for implementation of the moderate number of target mutations that already can guide treatments, the so-called "action-ome", and develop decision systems for clinical implementation of tumour mutation profiling.

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While adjuvant chemotherapy has improved long-term survival for many types of cancer, the fact that many patients relapse despite the best available treatment underlines the limitations of contemporary therapy. The mechanisms of chemoresistance in general are poorly understood; thus, we are unable to predict who will benefit or not from treatments. Over the last decades, a number of "targeted therapies" have been approved for certain histologically defined cancers. These therapies target defined markers ir phenotypes such as the HER-2 proto-oncogene; thus, they are effective only in cancers harboring certain gene aberrations. Notably, even among patients with tumor harboring the targeted defects, many may not respond to treatment, or eventually relapse. These findings underline the need for a wider mutation analysis to define the gene defects responsible also for drug resistance with respect to all forms of anticancer therapies. The accumulated data on tumour mutation spectra and outcome from traditio nal therapies will also yield important knowledge on which of the patients are likely to benefit from such therapy, and for whom other options need to be considered. Additionally, sequencing of the constitutional (normal) DNA will enable the identificatio n of predisposition to acute and late adverse effects. This project is a national collaboration among regional cancer centres as visioned by the National Coordination Group for Research in the Health Service (NSG). The main objective of this joint effor t is a national diagnostic service for all Norwegian cancer patients. In addition to the strong representation of clinical groups, we have involved some of strongest national networks in medical genomics, the Norwegian Microarray Consortium and the FUGE B ioinformatics Platform, with proven experience in the relevant deep sequencing of cancer mutations, as well as the CancerBioMedicine Centre of Excellence and the Norwegian Cancer Registry. There is also a strong int

Publications from Cristin

Activity:

BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering