Den Nasjonale Kre-u/ordringen Se# fra Kre)forskningsins0tu#et Gunnar Sæter Leder Ins/tu0 for Kre4forskning Oslo Universitetssykehus
Utviklingsbildet Økende antall kre-pasienter (+33% ;l ca. 40 000/år i 2030) Drama;sk økende biologisk forståelse Stadig oppdeling i mindre pasientgrupper basert på biologiske mekanismer, på tvers av tradisjonell inndeling Ny behandling som selek;vt og direkte angriper sykdomsbiologien i den enkeltes kre-sykdom Parallell utvikling av medikament og diagnos;sk/ predik;v test Ny metodologi for klinisk utprøving Krav ;l større sannsynlighet for effekt og større Kombinasjonsbehandling
Behandling av kre4ens generelle karakter Direkte angrep på kre4- biologisk nøkkelmekanisme i den enkelte svulst 100% 80% 60% Imatinib 40% 20% Pre-Imatinib 0% 0 1 2 3 4 5 Years After Registration Adapted from J-Y Blay, 2010
«Key» Cell Signalling Pathways. PI3K
Hva er relevant? Bioinforma;kk... Soma0c muta0on rate
The number of an;cancer drugs in clinical development is increasing www.esmo2012.org
Risikovegring - I laboratoriet - I klinisk utprøving PD-1 PD-1 BRAF BRAF AKT AKT mtor mtor mtor PARP PARP PARP PARP www.esmo2012.org
mrna expression profiling of locally advanced breast cancers A set of 550 genes were identified Sørlie, et al PNAS 2001 5 subgroups Perou, Sørlie et al; Nature 2000 7572 citations Sørlie, Perou et al; PNAS 2001 5874 citations Sørlie, Tibshirani et al; PNAS 2003 3332 citations PAM50 ROR test FDA-godkjent sept. 2013
Mer kunnskap Ny kunnskap Mer kunnskap Sette i sammenheng Innovasjon Kliniske studier - Implementering
Institutt for Kreftforskning
Ins;tute for Cancer Research Gunnar Sæter N~310 7 Departments, 28 Research Groups Dept. Tumour Biology G. Mælandsmo Dept. Biochemistry Harald Stenmark Dept. Radia;on Biology Kris/an Berg Dept. Gene;cs Anne- Lise Børresen Dale Dept. Cancer Preven;on Ragnhild Lothe Dept. Immunology Johanna Olweus Dept. Cell Biology Erik Boye Mælandsmo Molecular biol. of the metasta/c process, molecular aspects of targeted therapy Myklebost Molecular biology & gene/cs of sarcomas Meza- Zapeda Mol gene/cs & signaling in sarcomas & NSCLC, circ tumour DNA, deep seq, NSCLC pers. med. Flatmark Pre- clinical therapy models incl immunotoxins. Met biol incl, deep seq & pers Rx, biomarkers incl micromet & mirna Hovig Melanoma systems biology/modeling. Signaling crosstalk. Bioinforma/cs Taskén Role of Beta- 2 adrenergic receptor (ADRB2) in CRPC Stenmark Signalling in PI3K- Type III tumor supressor pathway, Kif5- Ret oncogenic fusion protein, cell membrane traffic, molecular cell biology through receptor signalling in drosophilia Wiedlocha FGFR signalling, FGF- cytotoxic conjugate as targeted therapy, Gene/c regula/on of normal cell migra/on and its rela/on to the metasta/c process Rofstad Pre- clinical personalized radiotherapy, markers of RT resistance, incl. hypoxia on MRI Berg PCI (& nanopar/cles) for intracellular drug delivery Moan PDT therapeu/cs, carcinogenesis of solar exposure, Vit D protec/on Børresen- Dale Large scale gene/c profiling/signatures & p53 signaling in BC, personalized treatm. lung ca Kure Molecular characteriza/on of resected pancrea/c & colorectal cancer, incl progn & predic/ve markers (mrna, mirna, serum glycans, SNPs) Lothe Transl research in CRC incl prognos/c biomarkers. Gene/cs of solid tumors Olweus Tumor- specific T- cell ac/va/on with tumor Ag & foreign or self HLA. T- cell engineering with tumor- specific TCRs Cellebiologi, signallering, transport Lyng Skotheim Prospec/ve Molekylærbiologi evalua/on of Kristensen Genome biology RT resistance mechanisms Epigene/cs, mirna, & transcriptome & biomarkers in clinical SNP, deep seq., copy variability in Sandvik cervical & prostate cancer number, func/onal tumor Malmberg Biodegradable Molekylærgene/kk, genomics in BC sekvensiering and OC development. NK cell diversity nanopar/cles in cancer Func/onal genomics as cancer Syljuåsen diagnosis & therapy, biomarker. Pre- clinical molecular Sørlie mechanisms & signalling mrna, lineage Iden/fica/on & Intracellular transport, Spredningsbiologi Lind expansion of ErbB regula/on, following RT- induced tracing & biomarkers Epigene/c bio- DNA damage. BC tumourigenesis NK subpop for Extracellular vesicle markers in CRC Genomic instability. & progression cancer therapy. content as Strålingsbiologi NK CAR engineering Influence of hypoxia biomarkers in cancer (prostate as model) Stokke Prognos/ske og predik/ve faktorer Cell cycle arrest in RT of haeme cells, biology of lymphoma, centrosome/ Tumorimmunologi/Immunterapi/Celleterapi cilia proteins, PARP inhib. Sioud Phage libraries for tumor pep/de discovery. DC ac/va/on through IDO downregula/on with sirna, stroma signalling manipula/on with sirna Smeland Lymphoma/B- cell biology. Lymphoma profiling, including risk profile for transforma/on to DLBCL Boye Cell cycle regula/on in yeast Skarstad Regula/on of replica/on & genomic instability in E coli
New Era of Immunotherapy
Samarbeid Samhandling
På forskningsnivå / Ins/tu0- nivå Tidligere paradigme: Klinisk praksis Basal Translasjon Klinisk Outcomes Research Ny0 paradigme: Strategisk dedikasjon
På ins/tusjonsnivå Basic research Ins;tusjonell dedikasjon Infrastruktur Comprehensive Cancer Center Epidemiologic research Clinical research Pa;ent care
Omverdenen... Internasjonale Fagmiljøer Fokuserte prosjekter Store grupper/ne#verk EU NCI Biotech Big Pharma OCC Program- samarbeid Kre-foreningen NFR Regionale HF SLV REK Pasient- organisasjoner Nasjonale Fagmiljøer Nasjonale tumorgrupper Universitetene Universitetssykehusene