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2012 © Institute for Molecular Medicine Finland FIMM

Genome-scale cancer biology and personalized cancer medicine

We are integrating genomic profiling, high-throughput RNA interference and chemical biology data to investigate the molecular basis of human breast and prostate cancer. These bioinformatic and systems biological studies of cancer are coupled with translational research on the responses of cancer cells to drugs as well as the molecular features of biobanked human tumour cohorts.

The aim is to combine the understanding of the molecular pathogenesis of cancer with the patterns and pathways that play a role in anti-cancer drug response. This should make it possible to develop synergistic combinatorial strategies to block the “escape routes” of cancer. This approach is also providing an exciting ability to generate rapidly actionable personalized medicine strategies for the clinical treatment of cancer patients.

In order to promote translational opportunities, we have recently shifted our interests to studies of human leukaemias as a model to advance the personalized
medicine of cancer. In collaboration with Jonathan Knowles/Caroline Heckman
and Krister Wennerberg at FIMM, as well as Kimmo Porkka and the Finnish Hematology
Association, we are using high-throughput ex-vivo drug sensitivity testing
to leukemic cells, coupled with the molecular profiling of the cancer cells by
RNAseq, exome-seq, and phosphoproteomics. We believe that the implementation
of these types of personalized molecular and functional profiles is possible in
the management of human leukaemias today, while it may take several years to
achieve similar translational progress for the common solid tumours.

Selected publications:

• Edgren H, Murumägi A, Kangaspeska S, Nicorici D, Hongisto V, Kleivi K, Rye IH, Nyberg S, Wolf M, Borresen-Dale AL, Kallioniemi O. Identification of fusion genes in breast cancer by paired-end RNA-sequencing. Genome Biol. 12(1):R6, 2011

• Östling P, Leivonen SK, Aakula A, Kohonen P, Mäkelä R, Hagman Z, Edsjö A, Kangaspeska S, Edgren H, Nicorici D, Bjartell A, Ceder Y, Perälä M, Kallioniemi O. Systematic Analysis of MicroRNAs Targeting the Androgen Receptor in Prostate Cancer Cells. Cancer Res. 71(5):1956-1967, 2011.

• International Cancer Genome Consortium, Hudson TJ, et al. International network of cancer genome projects. Nature, 464(7291):993-998, 2010.

• Iljin K, Ketola K, Vainio P, Halonen P, Kohonen P, Fey V, Grafström RC, Perälä M, Kallioniemi O. High-throughput cell-based screening of 4910 known drugs and drug-like small molecules identifies disulfiram as an inhibitor of prostate cancer cell growth. Clinical Cancer Res. 15(19):6070-8, 2009.

• Kilpinen S, Autio R, Ojala K, Iljin K, Bucher E, Sara H, Pisto T, Saarela M, Skotheim R, Björkman M, Mpindi JP, Haapa-Paananen S, Vainio P, Edgren H, Wolf M, Astola J, Nees M, Hautaniemi S, Kallioniemi O. Systematic bioinformatic analysis of expression levels of 17,330 human genes across 9,783 samples from 175 types of healthy and pathological tissues. Genome Biol. vol. 9:R139, 2008.

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