Cancer development is a multi-step process that leads to uncontrolled tumour cell growth caused by and resulting in complex changes: many genes are amplified, deleted, mutated, up- or down-regulated, many pathways are activated or suppressed.Estimating from the CONCORD study across 1.9 million patients from 31 countries and 5 continents, current treatments achieve a 5-year survival rate for less than 50% of diagnosed cancer (Coleman, 2008). Approximately 12.7 million new cancer cases were diagnosed worldwide in 2008. Lung, female breast, colorectal & stomach cancers account for more than 40% of all cases. Almost 8 million deaths from cancer occurred worldwide in 2008. Lung, stomach, liver, colorectal & female breast cancers account for more than 50% of all cancer deaths (http://www.cancerresearchuk.org/cancer-info/cancerstats/world/).

Canadian cancer statistics (2012) indicates that lung cancer accounts for almost 14% of all cancer cases in Canada, leading to the highest number of deaths (20,100, 27% of all cancers). Years of research improved relative survival by 6% for all cancers since 1992. Highest improvements are for non-Hodgkin lymphoma & leukemias. Success in breast and prostate cancers has been achieved by finding molecular markers for early diagnosis and by individualized treatment. Highest survival is for thyroid, prostate & testicular cancers. However, pancreatic cancer remains almost 100% lethal, and the overall survival rate for lung cancer has improved barely during the past decades, having only moved from 13% to 16%.

Cancer is caused by genetic changes or environmental effects that interfere with the mechanisms that control cell growth. These changes, as well as normal cell activities, can be detected in tissue samples through the presence of unique indicators, such as DNA and proteins, which together are known as “markers.” Specific combinations of these markers may be associated with a given type of cancer, indicate patient's risk of cancer recurrence, or indicate probability of patient's response to treatment. While several markers are already known to be associated with certain cancers, there are many more to be discovered, as cancer is highly heterogeneous.

The discovery and validation of biomarkers is complex and computationally intensive process. It involves analyzing hundreds of thousands of parameters (clinical variables, gene, protein, microRNA, activity, etc.) to identify subsets that best describe patients, their prognosis and response to treatment. Finding all clinically useful markers and selecting the best subset represents a challenging computational optimization task as we would need to compare all possible parameter combinations.

The Mapping Cancer Markers (MCM) project focuses on clinical application - discovering specific groups of markers that can be used to improve detection, diagnosis, prognosis and treatment of cancer. As a second goal, the comprehensive analysis of existing molecular profiles of cancer samples will lead to unraveling characteristics of such groups of markers - and in turn improving our understanding how to find them more efficiently.

Our strategy to reduce mortality includes three steps:

• Increase number of cases diagnosed at earlier stage
  • We need to identify biomarkers for early cancer detection
• Individualized treatment
  • We need to find biomarkers for treatment selection and response monitoring
• Improved treatment
  • We need to improve our understanding of disease mechanism and drug mechanism of action
  • We need to identify useful drug combinations and design new medicines

• Coleman, M. P., M. Quaresma, et al. (2008). "Cancer survival in five continents: a worldwide population-based study (CONCORD)." Lancet Oncol 9(8): 730-756.
• Ein-Dor, L., I. Kela, et al. (2005). "Outcome signature genes in breast cancer: is there a unique set?" Bioinformatics 21(2): 171-178.
• Ein-Dor, L., O. Zuk, et al. (2006). "Thousands of samples are needed to generate a robust gene list for predicting outcome in cancer." Proc Natl Acad Sci U S A 103(15): 5923-5928.