Cancer Biology & Epidemiology

Biological Causes of Cancer

• Avoiding immune destruction
• Evading growth suppressors
• Enabling replicative immortality
• Tumor-promoting inflammation
• Activating invasion and metastasis
• Genomic instability
• Inducing angiogenesis
• Resisting cell death
• Deregulating cellular energetics
• Sustaining proliferative signaling

Nomenclature

• Benign: -oma
• Malignant epithelial tissue: -carcinoma
• Malignant connective tissue: -sarcoma
• Fatty tissue: lip-
• Gland tissue: adeno-
• Fibrous tissue: fibro-
• Bone: osteo-
• Cartilage: chondro-
• Blood vessel: hemangio-
• Smooth muscle: leiomyo-
• Striated muscle: rhabdomyo-

Special Nomenclature

• Hodgkin’s lymphoma
• Wilms’ tumor
• Ewing sarcoma
• Melanoma → malignant
• Heptamoa → carcinoma

Molecular Basis of Cancer

• 2 genes, 1 that promotes, 1 that represses; when either one is defective, they both cause uncontrolled cell growth
• Signaling genes:
  • Proto-oncogenes (RAS, MYC); normal cell proliferation
  • Oncogenes (oncoproteins); mutated proto-oncogenes, uncontrolled cell growth
• DNA repair genes:
  • BRCA1: chromosome 17
  • BRCA2: chromosome 13
  • Can be spontaneous or heritable
• Apoptosis genes:
  • BAX
  • BCL-2
  • These are defective cells that favor cell survival when it should be programmed cell death

Tumor Suppressor Genes

Regulate cell cycle, inhibit cell proliferation, stop cell division, and prevent mutations (normally)

• Governors: prevent bad things from happening, but the “brake” on
• Guardians: like the police, tag the bad things, and monitor; damage control
  • P53, APC

Angiogenesis

Growth of new vessels

• Vascular endothelial growth factor (VEGF)
• Cancer can create new routes of energy/life for itself so it creates more blood vessels to keep it alive
• Avastin stops the growth of blood vessels

%%Warburg Effect%%

• Use of glycolysis under normal oxygen conditions, aerobic glycolysis and oxidative phosphorylation
• For every 1 glucose = 1 ATP; completely shuns the mitochondria
• Allows rapid cell growth
• Activated by oncogenes and mutant tumor suppressors

==Reverse Warburg Effect==

• @@LACTATE = LAZY@@
• Doesn’t shun the mitochondria
• Tumor cells can demand for other cells to make extra @@lactate@@ to keep them fed, hence, reprograms the other cell’s metabolism
• Makes other cells do the work for the tumor

The 1-5 Year Survival:

• A patient comes in and the cancer is removed surgically
  • After surgery, day 0 begins
• If the cancer came back within 1 year, the chance of survival from the specific cancer is lowered
• If the cancer did NOT come back, there is a higher chance of survival to 5 years

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Staging

How far has the cancer spread?

• Stage I: No metastasis
• Stage II: Local invasion
• Stage III: Spread to regional structures
• Stage IV: Distant metastasis

%%★ Universal system%%

• T: Tumor spread (T-T3)
• N: Node involvement (N-N2)
• Metastasis: Metastases (M-M2)

Staging Colon Cancer

• Duke’s A: stage I, no metastasis
  • 5 yr survival >90%
• Duke’s B: stage II, local invasion
  • 5 yr survival 55% to 85%
• Duke’s C: stage III, spread to regional structures
  • 5 yr survival 20% to 55%
• Duke’s D: stage IV, distant metastasis
  • 5 yr survival <5%

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Grading

How bad do the cells look?

• %%Low grade/grade I:%% well differentiated, normal tissue
• Intermediate/grade II: moderately differentiated
• High grade/grade III: poorly differentiated, may begin to act more aggressively
• ==High grade/grade IV:== undifferentiated, high degree of anaplasia

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Clinical Manifestations of Cancer

• Anemia
• Fatigue
• Cachexia
• Leukpenia
• Thrombocytopenia
• Infection
• Skin and hair changes
• GI manifestations
• Paraneoplastic symptoms

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Warning Signs of Cancer

1. Unusual bleeding
2. Changes in bowel or bladder habits
3. Change in a wart or mole
4. A sore that does not heal
5. Unexplained weight loss
6. Anemia, low hemoglobin, persistent fatigue
7. Persistent cough, hoarseness without reason
8. A solid lump, often painless (most commonly in the breast or testes)

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TNM Staging

• T: Tumor spread
  • T0= breast free of tumor
  • T1= lesion <2cm
  • T2= lesion 2-5 cm
  • T3= skin/chest wall involved by invasion
• N: Node involvement
  • N0= no axillary nodes involved
  • N1= mobile nodes involved
  • N2= fixed nodes involved
• M: presence of distant metastasis
  • M0= no metastases
  • M1= demonstrated metastases
  • M2= metastases confirmed

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