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1、Discovery of Cancer Biomarkers张敏跃南京大学生命科学院StatisticsMore than 11 million people are diagnosed with cancer every year. It is estimated that there will be 16 million new cases every year by 2020. From a total of 58 million deaths worldwide in 2005, cancer accounts for 7.6 million (or 13%) of the globa
2、l mortality. Deaths from cancer in the world are projected to continue rising, with an estimated 9 million people dying from cancer in 2015 and 11.4 million dying in 2030. In the US in 2006, over 1.4 million new cases of cancer were diagnosed. Over half a million people died from this disease, accou
3、nting for approximately 25% of all deaths in the US each year How to Improve the Situation? Prevention Detection Cancer is a disease of genetic progression that is often associated with specific molecular, genetic and histological changes. The ability to develop biomarkers that can detect the critic
4、al components of these hallmarks of cancer together provides a powerful basis for diagnosing, monitoring and predicting outcome and response to treatment.How to Improve the Situation? The goal of cancer biomarker field is to develop simple non-invasive tests that indicate cancer risk, allow early ca
5、ncer detection, classify tumors so that the patient can receive the most appropriate therapy and monitor disease progression, regression and recurrence. 3. TreatmentConcept of Cancer BiomarkersDefinition of biological markers Biological markers (biomarkers) have been defined by Hulka and colleagues
6、(1990) as “cellular, biochemical or molecular alterations that are measurable in biological media such as human tissues, cells, or fluids.” Hulka BS. Overview of biological markers. In: Biological markers in epidemiology (Hulka BS, Griffith JD, Wilcosky TC, eds), pp 315. New York: Oxford University
7、Press, 1990. More recently, the definition has been broadened to include “biological characteristics that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention ”Naylor S. Biomarkers:
8、current perspectives and future prospects. Expert Rev Mol Diagn 3:525529, 2003.Concept of Cancer Biomarkers2. Forms of cancer markers Hormones, metabolites，as well as different functional subgroups of proteins such as enzymes, glycoproteins, oncofetal antigens and receptors. Furthermore, other chang
9、es in tumors, such as genetic mutations, amplifications or translocations, and changes in microarray-generated profiles (genetic signatures), are also forms of tumor markers. The markers are produced either by the tumor itself or by other tissues, in response to the presence of cancer or other assoc
10、iated conditions, such as inflammation. Cancer biomarkers can also be processes such as apoptosis, angiogenesis or proliferation.Concept of Cancer Biomarkers3. Factors that are ideal for a tumor marker Produced by the tumor cells and enters the circulation Present at low levels in the serum of healt
11、hy individuals and those with benign disease but increases substantially in cancer (preferably in one cancer type only) Easily quantifiable with an inexpensive assay Present in detectable (or higher than normal) quantities at early or preclinical stages Quantitative levels of the tumor marker reflec
12、t the tumor burden High diagnostic sensitivity (few false negatives) and specificity (few false positives)Concept of Cancer Biomarkers3. Factors that are ideal for a serological tumor markerConcept of Cancer Biomarkers4. Types of cancer biomarkers 4.1. Diagnostic (screening) biomarker A marker that
13、is used to detect and identify a given type of cancer in an individual. These markers are expected to have high specificity and sensitivity For example, the presence of Bence Jones protein in urine remains one of the strongest diagnostic indicators of multiple myelomaConcept of Cancer Biomarkers4.2.
14、 Prognostic biomarker This type of marker is used once the disease status has been established. These biomarkers are expected to predict the probable course of the disease including its recurrence, and they therefore have an important influence on the aggressiveness of therapy. For example, in testi
15、cular teratoma, human chorionic gonadotropin and alfa-fetoprotein levels can discriminate two groups with different survival rates.Concept of Cancer Biomarkers4.3. Stratification (predictive) biomarker This type of marker serves to predict the response to a drug before treatment is started. This mar
16、ker classifies individuals as likely responders or nonresponders to a particular treatment. These biomarkers mainly arise from array-type experiments that make it possible to predict clinical outcome from the molecular characteristics of a patients tumor.Current applications of tumor markers and their limitationsCurrent applications of tumor markers and their lim
