Biology of Cancer Carcinogenesis Detection Prevention. Kerry Hennessy MSN, RN, AOCN

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1 Biology of Cancer Carcinogenesis Detection Prevention Kerry Hennessy MSN, RN, AOCN

2 The Impact of Cancer Cancer is a major public health problem. One in four U.S. deaths due to cancer.* Cancer has surpassed heart disease in being the number one disease killer of Americans under the age of 85 since Places a high economic burden on society.* * Jemal, A. et al. CA-A Cancer Journal for Clinicians. 55 (1), 10.

3 CHARACTERISTICS OF CELLS Regular size and shape Function Predictable life span Genetic programming Responsive to bio feedback mechanisms Apoptosis

4 EXAMPLE OF NORMAL CELL GROWTH Dead cells shed from outer surface Epidermis Dividing cells in basal layer Dermis

5 NORMAL CELL REPLICATION Growth factor Normal Growth-Control Pathway Receptor Signaling enzymes Transcription factors Cell nucleus DNA Cell proliferation

6 CELL REPLICATION Occurs billions of times every 24 hours to replace damaged or worn out cells or produce proteins that support life Process turned on by growth factors Driven and moderated by genes Repair genes Surveillance genes Killer (suppressor) genes Further surveillance of damaged cells by immune system

7 Proto-Oncogenes and Normal Cell Growth Normal Growth-Control Pathway Growth factor Receptor Signaling enzymes Transcription factors Cell nucleus DNA Cell proliferation

8 DNA Repair Genes Normal DNA repair T C G A C Base pair mismatch No cancer T C T A C A G C T G T C T A C T C T A C A G C T G Cancer A G T G A G A T G No DNA repair

9 Tumor Suppressor Genes Act Like a Brake Pedal Growth factor Tumor Suppressor Gene Proteins Receptor Cell nucleus Signaling enzymes Transcription factors DNA Cell proliferation

10 p53 Tumor Suppressor Protein Triggers Cell Suicide p53 protein Normal cell Excessive DNA damage Cell suicide (Apoptosis)

11 Immune Surveillance As tumor cells differentiate, they produce proteins or antigens expressed on the cell surface Immune system recognizes these cells as non-self An immune response is mounted in defense Through a variety of mechanisms, the immune system destroys the foreign/non-self object (NK cells, cytotoxic T Cells, etc.) Tumors can develop if they evade Immune surveillance

12 Normal Cell Function 101 all cells come from preexisting cells vital functions of an organism occur within cell all cells contain the hereditary information necessary for regulating cell functions and for transmitting information to the next generation of cells.

13 HOW CANCER CELLS DIFFER FROM NORMAL CELLS DNA errors Reproductive errors Dedifferentiation Uncontrolled proliferation

14 Normal Vs. Malignant

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16 Properties of Cancer Cells Cytological changes Size and number Nuclear/cytoplasmic ratio Altered cell growth Immortality Growth inhibition/cell cycle control Cell membrane changes New antigens

17 MALIGNANT TUMOR DEVELOPMENT RANDOM ABBERANCY 2. GROWTH AND INVASION 3. INTRAVASATION 4. METASTASIS

18 Malignant Transformation Initiation cell type specific Chemical/radiation/etc. Promotion Proliferation free for all Dysplasias, CIS Progression

19 Metastatic Disease Detachment Invasion Survival in transport Arrest in distant organ Establishment of secondary tumor

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21 Epidemiology Surveillance, Epidemiology and End Results patient demographics, primary tumor site, tumor morphology and stage at diagnosis, first course of treatment, and follow-up for vital status Almost 50% percent of the US population

22 Fast Stats Cancer Site Compare statistics for selected cancer sites. Race/Sex Compare cancer statistics by both race and sex. Race/Ethnicity Compare cancer statistics by race or by the expanded race/ethnicity groupings. Age at Diagnosis/Death Compare statistics by age groups for a selected cancer site, race, and sex. Sex Compare the differences between male and female cancer statistics. Data Type Compare Incidence, Delay-adjusted Incidence and Mortality cancer statistics.

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25 Risk Risk Factor Absolute Risk Relative Risk Odds Can you change the numbers???

26 RISK FACTORS FOR MALIGNANCY Non-modifiable Heredity Age Modifiable Life style Environment

27 LIFE STYLE RISK FACTORS Diet Exercise Substance use Viruses Radiation Chemicals Radiation exposure Chemical exposure

28 HOW DOES A MALIGNANT PROCESS EVOLVE? Genetics Hormones Environmental factors Chemical exposure Radiation Viruses Bad luck

29 Terminology Incidence Mortality Prevalence Survival Lifetime Risk Descriptive vs. Analytic

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31 Causes of Cancer Tobacco Environmental Tobacco smoke Workplace, home Diet Acrylamide (potato chips, french fries) Red and processed meats/high fat Artificial Sweeteners? Alcohol

32 Causes of Cancer Occupation Pollution Radiation Ionizing Non-ionizing Hormones

33 Causes of Cancer Viral Hepatitis HPV HIV EBV HTLV-1 Genetics Heredity Oncogenes Suppressor Genes

34 Detection Screening Happenstance

35 Screening Guidelines-ACS Colorectal Skin Breast Cervical Testicular Prostate Lung

36 When to look closer Change in bowel/bladder habits Unusual bleeding/discharge Sore that doesn t heal Mole or wart change Thickening or lump Nagging cough or hoarseness Indigestion/swallowing difficulty

37 Found something, what now? Lab Imaging Invasive Procedures

38 LAB Radioimmunoassay Tumor markers Enzymes Hormones Metabolic products Proteins antigens Flow cytometry DNA Cell surface markers

39 TUMOR MARKERS Biological substances used to guide and monitor treatment and potential disease activity CEA (carcinoembryonic antigen) PSA (prostate specific antigen) CA-125 (cancer antigen 125) CA15.3 (cancer antigen 15.3) AFP (alfa fetoprotein)

40 Imaging Xray Lung Surveillance/initial detection PET Benign/malignant guidance for bx MRI CT

41 Xray

42 CT Scan

43 Magnetic Resonance Image

44 Positron Emission Tomography

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46 Invasive Procedures Endoscopy Biopsy Surgical Excisional incisional Needle FNA Core Vacuum

47 TYPES OF CANCER TUMORS Carcinoma Adeno Squamous cell Sarcoma Osteo Myo Rhabdo Leio Lipo Chondro Hemangio Hematologic tumors Lympho Myelo Unknown primary

48 Tumor Nomenclature Tissue of Origin Benign vs. malignant Solid Epithelial Mesenchymal Neural mixed Hematologic

49 Staging And Grading WAYS TO CHARACTERIZE TUMOR GROWTH AND PROGNOSIS Anatomic Staging Degree of spread Grading Degree of cell dedifferentiation

50 TNM STAGING SYSTEM Determination of how extensive the malignancy is T = tumor size (also depth of invasion) N = nodal status (number and location of positive LN) M = metastatic disease

51 TNM STAGING

52 Staging of Hematologic Malignancies Lymphoma Leukemia Multiple Meyloma

53 Grading GX - undetermined G1 well differentiated, low grade G2 moderately differentiated, intermediate grade G3 poorly differentiated, high grade G4 undifferentiated, high grade

54 Tumor Grading 100% General Relationship Between Tumor Grade and Prognosis Low grade Patient Survival Rate High grade Years

55 Much needed info! Tissue of origin Biological behavior Cell differentiation Hetero- vs. Homogeneity Mitotic count Vascularization

56 Prevention Screening Risky behavior modification Nutrition Chemoprevention

57 ACS screening guidelines Colorectal 50 Colonoscopy every 10 years FOBT yearly Breast 40 Yearly mammogram Yearly CBE Prostate DRE PSA?

58 Cervical ACS screening guidelines 21 PAP every 3 years Lung 30 pack year Low dose CT

59 Chemoprevention is the use of pharmacologic or natural agents that inhibit the development of invasive cancer either by blocking the DNA damage that initiates carcinogenesis or by arresting or reversing the progression of premalignant cells in which such damage has already occurred. Tamoxifen, aspirin

60 More Information National Cancer Institute American Cancer Society