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ROLE OF TUMOUR MARKERS IN CANCER MANAGEMENT. PROFESSOR V. K. GOLAKAI BSc, MD, ChM, FWACS, FICS, DSc(Med) PRINCESS MARINA HOSPITAL. DEFINITION. Glyco- / lipoproteins produced by: malignant cells normal cells in response to tumour inflammatory cells and tissues
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ROLE OF TUMOUR MARKERS IN CANCER MANAGEMENT PROFESSOR V. K. GOLAKAI BSc, MD, ChM, FWACS, FICS, DSc(Med) PRINCESS MARINA HOSPITAL
DEFINITION Glyco- / lipoproteins produced by: • malignant cells • normal cells in response to tumour • inflammatory cells and tissues • found in serum, urine, body fluids • react with man-made antibodies or • combine with man-made antigens • cyto- / histo-compatibility reaction to form • cyto- / histocompatibility complexes
TYPES OF TUMOUR MARKERS • Tumour-Associated Proteins (TAP) • Cell membrane receptors • Hormones • Immunoglobulins / Cellular antigens • Polyamines • Protein clusters and fragments • Chromosomal material • Genes (single, clusters) • Genetic material (DNA, RNA, mRNA) • Cell modulators (transducers / suppressors)
Specific Classes of TM’s • Enzymes (PSA, NSE, VMA, HVA) • Cell membrane receptors (ER, PR) • Tumour antigens (CEA, AFP) • Antibodies (IgA, IgG, IgM, IgD) • Antigens (p53, ki-62) • CA-specific proteins(CA 19-9, CA 124) • Gene mutation products (BR CA 1, 2)
Specific Classes of TM’s (2) • Tissue-specific proteins (PSA, hCGH) • Special hormones (b-hCGH, h-CGH) • Catecholamines (VMA, HVA, ACTH) • Polyamines • Cytoplasmic / Nucleic material (DNA) • Products of cell turn-over (TNF) • Cellular modulators (ki-62, c-erb-2)
WHO CRITERIA (1) [968] • Important role in evaluation • Role must be well understood • Role must be recognized • Can be tested early • Detects treatment response
WHO CRITERIA (2) [1968] • Support for test available • Support / treatment beneficial • Benefits greater than side-effects • Screening must be cost-effective • Detect / diagnose malignant disease
Types of test kits • ELISA Test Kits • Immuno-histochemical kits (ICH) • Polymerase chain reaction (PCR) • Cluster Kits ( All-in-One Kit) • Detects profiles • Patterns • Prototypes • Constellations
METHODS OF ANALYSIS • Expression of single proteins • Expression of multiple proteins • Chip analysis – “All-in-One” • Expression of protein profiles (Proteonomics) • Gene methylation at DNA level • Genes / mutations (Genomics) • G-scan (genome ID scan)
hCGH (specific) beta-hCGH dto CEA (NS) AFP (NS) Bence-Jones (MM) Beta-2-M (S) BTA (Bladder) (S) CgA (Chromogranin-A) CA-15-3 (NS) CA-19-9 (NS) CA-72-4 (NS) CA-27.29 (NS) CA-125 (NS) ER / PR (Breast) HER-2 neu (c-erbB-2) BR CA-1 / BR CA-2 COMMON TUMOUR MARKERS IN CLINICAL PRACTICE
LASA-P (S) NM-22 (S) PSA (Prostate-S) PSMA (Prostate-S) S-100 (Melanoma) TA-90 (NS) TgA, IgA, D, G, M TPA (NS) Alk. p’tase (mets) Alpha Amylase SIADH, ACTH, ADH GT-II (NS) VMA, HVA (S) Polyamines (NS) Genes (k-ras, ki-62) Chromosome (p53) COMMON TUMOUR MARKERS IN CLINICAL PRACTICE (2)
Clinical uses of TM’s • Screening populations at risk • Early detection of tumour • Diagnosing and aiding diagnosis • Predicting response to treatment • Monitoring patients with cancer
Clinical uses of TM’s (2) • Assessing prognosis in cancer • Differentiating malignant v benign • Predicting / detecting recurrence • Evaluating extent of disease • Targeting localisation & therapy
Short-comings of TM’s • TM’s are not specific enough • TM’s are not sensitive enough • Not produced by cancer cells alone • TM’s are not ideal for evaluating CA • Poor detectors / predictors early CA • Not good enough prognosticators • TM testing hindered by “Hook effect”
NEW FRONTIERS • Genomics – Gene structure • Proteonomics – Protn structure • Pharmacogenomics – Gene-based drugs structuring and delivery • G-scan – Human genome mapping • New treatment modalities • Individualised treatment modalities • Early detection of malignant change • Greater sensitivity and specificity • Better monitoring and follow-up care
PHARMACOLOY BRAVE NEW SCIENCE Protein based drugs Stem cell biology GENETIC REVOLUTION TM DNA-Genome PROTEONOMICS CYTOGENES Gene chips G scan Antibiotics, antimicrobials PHARMACO GENETIC TESTS PERFECT HEALTH REGENERATIVE MEDICINE DISEASE DEATH PROCREATION IMORTALITY/LOGNGEVITY BIRTH REGENERATIVE MEDICNE GERM-LINE GENOMICS HUMAN TRAIT ALTERATIONS
REGENERATIVE MEDICINE: BRAVE NEW WORLD • Instead of cutting flesh with steel and poisoning the body with chemicals or burning it with radiation; • Physicians would gently treat the body with nothing but proteins and cells, seeking to mend like with like. • Instead of depending only on his knowledge and limited and erratic skills snf methods; • Physicians would seek to tap information in the genome and to exploit the fact that the body’s cells are designed to be a self- modulating self-assembling system when given proper signals. • Instead of sending a patient home merely patched up enough to live with simmering uncured disease or decaying cells; • The physician would not rest until the damaged tissues were replaced with ones as good as new, if not better.