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

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%

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

Clinical Manifestations of Cancer

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

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)

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