Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine

Photo: Jarle Bruun

Guro E. Lind

Department of Cancer PreventionRagnhild A. Lothe group

Cancer BiomedicineUniversity of Oslo

Biomarkers for non-invasive testing for colorectal cancer

Photo: Jarle Bruun

”Life sciences for health and innovation” Oct 11th 2011, Oslo

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine Early diagnosis will improve patient survival

Illustration is modified from National Cancer Institute

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine Early diagnosis will improve patient survival

Illustration is modified from National Cancer Institute

90%

81%

63%

9%

Survivial: data from the Norwegian Cancer Registry, 2009

SU

RV

IVA

L 5

yea

rs

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine ”Window of opportunity” for diagnostics

Normalmucosa

CarcinomaIntermed.adenoma

Smalladenoma

Largeadenoma

Diagnostics5-35 years

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine

FOBT = fecal occult blood testWell established, simple, reduce mortality of CRC

Unspecific, limited sensitivity, and limited detection of precursors (adenomas)

Blood/plasma/serum test-Epi ProColon test. Methylation marker, SEPT9.

Fecal DNA testLimited sensitivity and specificity-The ColoSure test. Methylation marker, VIM

Need for additional tests/biomarkers

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine Project progress and time frame

Experimental pipeline Results

New strategy for identification of methylated candidates

Lind et al Cell. Oncol. 2006

Proof-of-principleLind et al Gastroenterology 2007

Clinical validation of first biomarker

Lind et al J Transl Med. 2008

Methylation in precursor lesionsAhlquist et al Mol Cancer. 2008

Panel of biomarkers publishedLind et al Mol Cancer. 2011

Analysis of biological functionLind et al Oncogene. 2011

Innovation/development

DOFI signed, patent application2007

PCT/EP2008PA published, WO 2008/102002

2008

R&D, TTOBiotech conferences 2009

MTA phase I-II signedEur Biotech comp 2010

License agreement? 2011

Six biomarkers identified

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine Clinical test and validation series

Normalmucosa

CarcinomaIntermed.adenoma

Smalladenoma

Largeadenoma

N = 61

Normal Benign

N = 51

Malignant

N = 80

Tes

t

N = 59 N = 105N = 52

Val

idat

ion

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine Biomarker performance

SensitivityAdenoma (n=111)

Carcinoma (n=179)

SpesificityNormal mucosa

n=110

93% 94%

98%

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine ROC confirms high sensitivity and specificty

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine

”Clinical proof of concept”: Non-invasive testing using fecal samples

Malignant

N = 72

CarcinomasFecal samplesBlood samples

Benign

N = 30

AdenomasFecal samplesBlood samples

N = 30

Normal mucosaFecal samplesBlood samples

Normal

NordICC screening

Oslo University Hospital Department of Cancer PreventionInstitute for Cancer Research

Radiumhospitalet

Centre for Cancer Biomedicine Collaborators

Cancer Registry• Dr. Michael Bretthauer

• Prof. Geir Hoff

Oslo University Hospital • Prof Arild Nesbakken • Dr. Espen Thiis-Evensen• Prof. Torleiv O. Rognum

Department of Cancer Prevention • Prof. Ragnhild A. Lothe Group leader and head of Department

• Stine A. Danielsen• Hilde Honne

www.rr-research.no/cancerprevention