Biology of Cancer

1. Biology of Cancer Chapter 11

2. Cancer • Derived from Greek word for crab, karkinoma • Malignant tumor • Tumor • Also referred to as a neoplasm—new growth

3. Benign vs. Malignant Tumors

4. Classification and Nomenclature • Benign tumors • Named according to the tissues from which they arise, and include the suffix “–oma” • Lipoma • Glioma • Leiomyoma • Chondroma

5. Classification and Nomenclature • Malignant tumors • Named according to the tissues from which they arise • Malignant epithelial tumors are referred to as carcinomas • Adenocarcinoma and basal cell carcinoma • Malignant connective tissue tumors are referred to as sarcomas • Chondrosarcoma and osteosarcoma

6. Classification and Nomenclature • Cancers of lymphatic tissue are lymphomas • Cancers of blood-forming cells are leukemias • Carcinoma in situ (CIS) • Pre-invasive epithelial malignant tumors of glandular or epithelial origin that have not broken through the basement membrane or invaded the surrounding stroma

7. Classification and Nomenclature

8. Classification and Nomenclature

9. Cancer Cells • Transformation • Cancer cell’s independence from normal cellular controls • Anchorage independent • Immortal • Anaplasia • Pleomorphic

10. Cancer Stem Cells • Stem cells self-renew • Cell divisions create new stem cells • Stem cells are multipotent • Ability to differentiate into multiple different cell types

11. Cancer Stem Cells

12. Cancer Stem Cells

13. Tumor Markers • Tumor cell markers (biological markers) are substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urine • Hormones • Enzymes • Genes • Antigens • Antibodies

14. Tumor Markers • Tumor markers are used to: • Screen and identify individuals at high risk for cancer • Diagnose specific types of tumors • Observe clinical course of cancer

15. Cancer-Causing Mutations • Cancer is predominantly a disease of aging • Clonal proliferation or expansion • Due to a mutation, a cell acquires characteristics that allow it to have selective advantage over its neighbors • Increased growth rate or decreased apoptosis • Multiple mutations are required before cancer can develop

16. Cancer-Causing Mutations

17. Types of Mutated Genes • Secretion of growth factors (autocrine stimulation) • Increased growth factor receptors • Signal from cell-surface receptor is mutated in the “on” position • Mutation in the ras intracellular signaling protein • Inactivation of Rb tumor suppressor • Activation of protein kinases that drive the cell cycle • Mutation in the p53 gene

18. Types of Mutated Genes

19. Angiogenesis • Growth of new vessels • Advanced cancers can secrete angiogenic factors

20. Hallmarks of Cancer

21. Telomeres and Immorality • Body cells are not immortal and can only divide a limited number of times • Telomeres are protective caps on each chromosome and are held in place by telomerase • Telomeres become smaller and smaller with each cell division

22. Telomeres and Immorality

23. Oncogenes and Tumor-Suppressor Genes • Oncogenes • Mutant genes that in their nonmutant state direct protein synthesis and cellular growth • Tumor-suppressor genes • Encode proteins that in their normal state negatively regulate proliferation • Also referred to as anti-oncogenes • Proto-oncogene • A normal, nonmutant gene that codes for cellular growth

24. Mutation of Normal Genes • Point mutations • Changes in one or a few nucleotide base pairs • Chromosome translocation • A piece on one chromosome is transferred to another • Gene amplification • Duplication of a small piece of chromosome over and over • Results in an increased expression of an oncogene

25. Mutation of Normal Genes

26. Mutation of Normal Genes

27. Mutation of Normal Genes • Mutation of tumor-suppressor genes • Allows unregulated cellular growth • Loss of heterozygosity • Both chromosome copies of a gene are inactivated • Gene silencing • Whole regions of chromosomes are shut off while the same regions in other cells remain active

28. Mutation of Normal Genes

29. Mutation of Normal Genes • Caretaker genes • Encode for proteins that are involved in repairing damaged DNA • Chromosome instability • Increased in malignant cells • Results in chromosome loss, loss of heterozygosity, and chromosome amplification

30. Inflammation and Cancer • Chronic inflammation is an important factor in the development of cancer • Cytokine release from inflammatory cells • Free radicals • Mutation promotion • Decreased response to DNA damage

31. Genetics and Cancer • Exposure to mutagens • If the mutation occurs in somatic cells, it is not passed to progeny • If the mutation occurs in germline cells, it can be passed to future generations

32. Viruses and Cancer • Implicated • Hepatitis B and C viruses • Epstein-Barr virus (EBV) • Kaposi sarcoma herpesvirus (KSHV) • Human papillomavirus (HPV) • Human T cell leukemia–lymphoma virus (HTLV)

33. Bacterial Cause of Cancer • Helicobacter pylori • Chronic infections are associated with: • Peptic ulcer disease • Stomach carcinoma • Mucosa-associated lymphoid tissue lymphomas

34. Environmental Risk Factors • Tobacco • Multipotent carcinogenic mixture • Linked to cancers of the lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix uteri, and myeloid leukemia

35. Environmental Risk Factors • Ionizing radiation • Emission from x-rays, radioisotopes, and other radioactive sources • Exposure causes cell death, gene mutations, and chromosome aberrations • Bystander effects • Poor gene repair • Changes in gap junction intercellular communication

36. Ionizing Radiation

37. Environmental Risk Factors • Ultraviolet radiation • Causes basal cell carcinoma, squamous cell carcinoma, and melanoma • Principal source is sunlight • Ultraviolet A (UVA) and ultraviolet B (UVB) • Promotes skin inflammation and release of free radicals

38. Environmental Risk Factors • Alcohol consumption • Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver cancers • Cigarette/alcohol combination increases a person’s risk

39. Environmental Risk Factors • Sexual reproductive behavior • Carcinogenic types of human papillomavirus • High-risk HPV • Physical activity • Reduces cancer risk • Decreases insulin and insulin-like growth factors • Decreases obesity • Decreases inflammatory mediators and free radicals • Increased gut motility

40. Environmental Risk Factors • Occupational hazards • Substantial number of occupational carcinogenic agents • Asbestos • Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc. • Radon

41. Environmental Risk Factors • Electromagnetic fields • Carcinogenic? • Are they, or aren’t they?

42. Environmental Risk Factors • Diet • Xenobiotics • Toxic, mutagenic, and carcinogenic chemicals in food • Activated by Phase I activation enzymes • Defense mechanisms • Phase II detoxification enzymes • Examples • Compounds produced in the cooking of fat, meat, or proteins • Alkaloids or mold by-products

43. Environmental Risk Factors • Obesity • Correlates with the body mass index (BMI) • Adipose tissue is active endocrine and metabolic tissue • In response to endocrine and metabolic signaling, adipose tissue releases free fatty acids • Increased free fatty acids gives rise to insulin resistance and causes chronic hyperinsulinemia • Correlates with colon, breast, pancreatic, and endometrial cancers