1. Cancer: when our own cells become the enemy
Erin Martinez, Ph.D.
Trevecca University
Physician Assistant Program
September 30, 2013

2. What is cancer? = a malignant tumor benign
= cells that escape their normal surroundings, invading locally and travelling to distant locations
= abnormal cell mass that develops when cells grow too much
benign

3. Moving from normal tissue to cancer
Normal cells
Benign tumor
Basement membrane
Blood vessel
Malignant tumor = CANCER
Bastid J, Ciancia C, Puisieux A, Ansieau S . Role of TWIST proteins in cancer progression. Atlas Genet Cytogenet Oncol Haematol. December

4. What does cancer look like?
Breast cancer: normal to cancer
Ductal carcinoma in situ
DeNardo and Coussens Breast Cancer Research :212

5. What does cancer look like? Colon cancer: normal to cancer
Tumor
Rose and Wu. The Internet Journal of Pathology. 12:

6. What does a cancer cell look like? The Hallmarks of Cancer
Cell Hanahan and Weinberg, 2000.

7. Hallmarks of Cancer: physiological changes1
Keeping the foot on the gas of growth 3 2
Cells don’t die easily
No brakes on growth! 5 6
Cells get more blood supply
Cells escape and spread 4
Cells divide forever, and ever…

8. Cell growth in cancer
Hallmarks 1 and 2: Keeping the foot on the gas of growth and no brakes on growth!
Progress though the cell cycle more quickly than a normal cell
Don’t follow normal rules for stopping the cell cycle (checkpoints)

9. Cancer cells resist death
Hallmark 3: Cells don’t die easily
Things that can usually cause programmed cell death (apoptosis)
DNA and protein damage
lack of nutrition/oxygen
buildup of waste
lack of survival signals from other cells
death signals from other cells
Cancer cells ignore these and survive!

10. Cancer cells are immortal
Hallmark 4: cells divide forever, and ever…
Normal cells stop growing or die when telomeres are gone
Cancer cells activate telomerase or do abnormal kinds of DNA recombination to survive!

11. Cancer cells induce angiogenesis
Hallmark 5: cells get more blood supply
Fast growing cells beginning to form a tumor need more nutrients and need to get rid of more waste than local blood vessels can provide
Promote formation of new blood vessels (angiogenesis) with signaling molecules (example: VEGF)

12. Cancer cells are on the move
Prostate cancer metastasis imaged with PET
Hallmark 6: cells escape and spread
Normal cells die when they loose contact with surrounding cells or the basement membrane
Cancer cells gain ability to migrate locally and sometimes flow through bloodstream and grow in a distant site (metastasis)
positron emission tomography (PET) scan
J Nucl Med February 2006 vol. 47 no

13. How do normal cells become cancerous?
Changes in gene expression and activity
most often caused by mutations
Mutations = changes in DNA that alter expression or activity of the gene
Two main types of genes with mutations in cancer:
Oncogene – genes that normally promote growth are mutated to be hyperactive
Tumor suppressor – genes that normally inhibit growth are mutated to be inactive
It takes several genetic alterations to cause cancer

14. How do we fight cancer? First surgery, then other therapies
Target fast-growing cells
- Radiation
- Chemotherapy
Kill all fast-growing cells - bad side effects

15. Other new cancer therapies
Anti-angiogenesis therapy
Avastin – anti-VEGF antibody for metastatic colorectal cancer, and advanced non-small cell lung cancer
Targeted therapy to a oncogene in a tumor cell
Gleevec - inhibitor of oncogene in chronic myelogenous leukemia
Erbitux – inhibitor of oncogene in colorectal and head/neck cancer
Herceptin - inhibitor of oncogene in breast cancer
Gleevec –BCR-Abl inhibitor
Erbitux – anti EGFR antibody
Herceptin – anti HER2/neu receptor
Activating immune system against cancer cells
Provenge – activate man’s own immune cells against prostate cells