1. Tumor Markers Lecture one By Dr. Waheed Al-Harizi

2. Objectives  To briefly introduce cancers, their incidence, some common terms, and staging system.  To be familiar with the definition of tumor markers, and characteristics of an ideal tumor marker.  To know various applications of tumor marker detection

3. Lecture outlines  Overview  Types of tumor markers  Applications of tumor marker detection: Screening Prognosis Monitoring effectiveness of therapy and disease recurrence

4. Overview  Cancer is the second leading cause of death in North America, accounting for > 500,000 deaths annually.  It is estimated that 45% of males and 38% of females will develop invasive cancer in their lifetime.  Although it is often specified as a single disorder, cancer is a broad term used to describe > 200 different diseases that affect ? 50 tissues

5. Overview, continued …  Biologically, cancer refers to the uncontrolled growth of cells that can develop into a solid mass or tumor & spread to other areas of the body.  The formation (tumorigenesis) & spreading (metastasis) of tumors are caused by a complex combination of inherited and acquired genetic mutations  During tumorigenesis, these mutations include activation of growth factors e.g. Epidermal Growth Factor (EGF) & oncogenes (e.g. K-ras), in combination with inhibition of apoptosis, tumor suppressor, and cell cycle regulation genes.

6. Overview, continued …  Cancer severity is generally classified by a combination of several factors.  Depending on the type of cancer, these factors include: Tumor size Histology Regional lymph node involvement The presence of metastasis  For most solid tumors (e.g., breast, lung, kidney), cancer is broadly classified (using roman numerals I- IV) into 4 stages

7. Common Cancer Terms AngiogenesisDevelopment of new blood vessels to supply oxygen and nutrients to cells ApoptosisProgrammed cell death Cell cyclePhases of cell activity divided into G, S, and M (growth, DNA synthesis, and mitosis, respectively) OncogeneEncodes a protein that, when mutated, promotes uncontrolled cell growth Tumor suppressor gene Encodes a protein involved in protecting cells from unregulated growth

8. Types of Tumor Markers  Cancer can be detected and monitored using biologic tumor markers.  Tumor markers are produced either directly by the tumor or as an effect of the tumor on healthy tissue (host).  Tumor markers encompass an array of diverse molecules such as: Serum proteins Oncofetal antigens Hormones Metabolites Receptors Enzymes

9. Estimated new cases of cancer and deaths from caner in USA MaleFemale TissueIncidenceDeathTissueIncidenceDeath Prostate29%9%Breast26%15% Lung15%31%Lung15%26% Colorectal10%9%Colorectal11%10%

10. Applications of Tumor Marker Detection  Ideally, a tumor marker would be: tumor specific absent in healthy individuals readily detectable in body fluids.  Unfortunately, all of the presently available tumor markers do not fit this ideal model.  However, a host of tumor markers have been identified that have a high enough specificity & sensitivity to be used in: screening populations at risk Diagnosis Prognosis Detection of recurrence Monitoring response to treatment.

11. Screening  With the possible exception of Prostate-Specific Antigen (PSA), no tumor marker identified to date can be used to adequately screen asymptomatic populations because most of the clinically used tumor markers are found in normal cells and benign conditions in addition to cancer cells.  Screening asymptomatic populations would therefore result in detection of false-positives-(patients without disease with detectable tumor marker), leading to undue alarm and cost to patients.  Presently, only a few tumor markers are used in populations with high incidence or other carefully defined populations.

12. Prognosis  Tumor marker concentration generally increases with tumor progression, reaching their highest levels when tumors metastasize.  Therefore, serum tumor marker levels at diagnosis can reflect the aggressiveness of a tumor and help predict the outcome for patients.  High serum tumor markers at diagnosis might indicate the presence of malignancy and possible metastasis associated with a poorer prognosis.  In other instances, the mere presence or absence of a particular marker may be valuable. Such is the case with some of the receptors used to base chemotherapeutic treatment in breast cancer.

13. Monitoring Effectiveness of Therapy and Disease Recurrence  One of the most useful applications of tumor markers is monitoring therapy efficacy and detecting disease recurrence.  After surgical resection, radiation, or drug therapy of cancer (chemotherapy), tumor markers are routinely followed serially.  In patients with elevated tumor markers at diagnosis, effective therapy results in a dramatic decrease or disappearance of the tumor marker.  If the initial treatment is effective, the appearance of circulating tumor markers can then be used as a highly sensitive marker of recurrence.