Understanding Cancer. Pankaj Kumar, MD

Transcription

1 Understanding Cancer Pankaj Kumar, MD

2 What Is Cancer?

3 Different Kinds of Cancer Some common carcinomas: Lung Breast (women) Leukemias: Bloodstream Lymphomas: Lymph nodes Colon Bladder Prostate (men) Some common sarcomas: Fat Bone Muscle

4 Naming Cancers Cancer Prefixes Point to Location Prefix Meaning adenochondroerythrohemangiohepatolipolymphomelanomyelomyoosteo- gland cartilage red blood cell blood vessels liver fat lymphocyte pigment cell bone marrow muscle bone

5 Loss of Normal Growth Control Normal cell division Cell damage no repair Cell Suicide or Apoptosis Cancer cell division First mutation Second mutation Third mutation Fourth or later mutation Uncontrolled growth

6 Example of Normal Growth Dead cells shed from outer surface Epidermis Cell migration Dividing cells in basal layer Dermis

7 Tumors (Neoplasms) Underlying tissue

8 Malignant versus Benign Tumors Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites Time

9 Why Cancer Is Potentially Dangerous Brain Liver Melanoma cells travel through bloodstream Melanoma (initial tumor)

10 Cancer Detection and Diagnosis

11 Early Cancer May Not Have Any Symptoms

12 Cervical Cancer Screening Normal Pap smear Abnormal Pap smear

13 Breast Cancer Screening

14 Prostate and Ovarian Cancer Screening

15 Colon Cancer Screening

16 Biopsy Pathology Proteomic profile Patient s tissue sample or blood sample Genomic profile

17 Tumor Staging 100% Five-Year Survival ates for Patients with Melanoma (by stage) 50% I II III Stage at Time of Initial Diagnosis

18 What Causes Cancer? Some viruses or bacteria Some chemicals adiation Heredity Diet Hormones

19 Population-Based Studies U.K.: Lung cancer egions of Highest Incidence JAPAN: Stomach cancer CANADA: Leukemia CHINA: Liver cancer U.S.: Colon cancer AUSTALIA: Skin cancer BAZIL: Cervical cancer

20 Heredity? Behaviors? Other Factors? 100 Colon Cancer (Number of new cases per 100,000 people) 100 Stomach Cancer (Number of new cases per 100,000 people) Japan Japanese families in U.S. U.S. 7 0 Japan Japanese families in U.S. U.S.

21 Tobacco Use and Cancer Some Cancer-Causing Chemicals in Tobacco Smoke

22 Low-Strength adiation High Dallas Skin Cancer Incidence Detroit Pittsburgh Low Least Annual Sunshine (UV radiation) Most

23 High-Strength adiation High Leukemia Incidence Low Least X-ray Dose (atomic radiation) Most

24 Lag Time 20-Year Lag Time Between Smoking and Lung Cancer 4000 Cigarette consumption (men) Cigarettes Smoked per Person per Year Lung cancer (men) Lung Cancer Deaths (per 100,000 people) Year

25 Viruses Cancer-linked virus Virus inserts and changes genes for cell growth

26 Examples of Human Cancer Viruses Some Viruses Associated with Human Cancers

27 AIDS and Kaposi s Sarcoma Without disease HIV infection Depressed immune system KSHV infection Kaposi s sarcoma

28 Bacteria and Stomach Cancer Patient s tissue sample H. pylori

29 Heredity and Cancer All Breast Cancer Patients Inherited factor(s) Other factor(s)

30 Heredity Can Affect Many Types of Cancer Inherited Conditions That Increase isk for Cancer

31 Genetic Testing

32 Cancer isk and Aging 400 Cancer isk and Aging Colon Number of Cancer Cases (per 100,000 people) Breast Age of Person (in years)

33 Genes and Cancer Viruses Chemicals adiation Heredity Chromosomes are DNA molecules

34 DNA Structure Chemical bases A C T G DNA molecule

35 DNA Mutation DNA C A A G C T A A C T Normal gene C A A G C G A A C T Single base change C A A G G C G C T A A C T Additions CA A G A A C T C T Deletions

36 Oncogenes Normal cell Normal genes regulate cell growth Cancer cell Oncogenes accelerate cell growth and division Mutated/damaged oncogene

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

38 Oncogenes are Mutant Forms of Proto-Oncogenes Inactive growth factor receptor Inactive intracellular signaling protein Signaling protein from active oncogene Activated gene regulatory protein Transcription Cell proliferation driven by internal oncogene signaling

39 Tumor Suppressor Genes Normal cell Normal genes prevent cancer emove or inactivate tumor suppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated tumor suppressor genes

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

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

42 DNA epair Genes Normal DNA repair T C G A C Base pair mismatch No cancer T C T A C AG C T G T C T A C T C T A C AG C T G Cancer A G T G A G A T G No DNA repair

43 Cancer Tends to Involve Multiple Mutations Benign tumor cells grow only locally and cannot spread by invasion or metastasis Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites Time Mutation inactivates suppressor gene Cells proliferate Mutations inactivate DNA repair genes Proto-oncogenes mutate to oncogenes More mutations, more genetic instability, metastatic disease

44 Mutations and Cancer Genes Implicated in Cancer

45 Cancer Tends to Corrupt Surrounding Environment Growth factors = proliferation Invasive Matrix Fibroblasts, adipocytes Proteases Blood vessel Cytokines Cytokines, proteases = migration & invasion

46 Cancer Prevention Carcinogenic radiation Carcinogenic chemicals Cancer viruses or bacteria

47 Avoid Tobacco 15x Lung Cancer isk Increases with Cigarette Consumption Lung Cancer isk 10x 5x Cigarettes Smoked per Day Non-smoker

48 Protect Yourself From Excessive Sunlight

49 Limit Alcohol and Tobacco Combination of Alcohol and Cigarettes Increases isk for Cancer of the Esophagus 40x isk Increase 30x 20x 10x Alcoholic Drinks Consumed per Day Packs of Cigarettes Consumed per Day AND

50 Diet: Limit Fats and Calories Correlation Between Meat Consumption and Colon Cancer ates in Different Countries 40 Number of Cases (per 100,000 people) Grams (per person per day)

51 Diet: Consume Fruits and Vegetables

52 Avoid Cancer Viruses High HPV Infection Increases isk for Cervical Cancer Cervical Cancer isk Low Noninfected women Women infected with HPV

53 Industrial Pollution Incidence of Most Cancers Year

54 Is There a Cancer "Epidemic"?