1. An Introduction to Cancer

2. US Mortality, 2003 No. of deaths % of all deaths Rank Cause of Death
1. Heart Diseases 685,
2. Cancer ,
3. Cerebrovascular diseases 157,
4. Chronic lower respiratory diseases 126,
5. Accidents (Unintentional injuries) 109,
6. Diabetes mellitus 74,
7. Influenza and pneumonia 65,
8. Alzheimer disease 63,
Nephritis ,
10. Septicemia ,

3. 2006 Estimated US Cancer Cases*
Men 720,280
Women 679,510
Prostate 33%
Lung & bronchus 13%
Colon & rectum 10%
Urinary bladder 6%
Melanoma of skin 5%
Non-Hodgkin % lymphoma
Kidney 3%
Oral cavity 3%
Leukemia 3%
Pancreas 2%
All Other Sites 18%
31% Breast
12% Lung & bronchus
11% Colon & rectum
6% Uterine corpus
4% Non-Hodgkin lymphoma
4% Melanoma of skin
3% Thyroid
3% Ovary
2% Urinary bladder
2% Pancreas
22% All Other Sites
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2006.

4. 2006 Estimated US Cancer Deaths*
Men 291,270
Women 273,560
Lung & bronchus 31%
Colon & rectum 10%
Prostate 9%
Pancreas 6%
Leukemia 4%
Liver & intrahepatic 4% bile duct
Esophagus 4%
Non-Hodgkin % lymphoma
Urinary bladder 3%
Kidney 3%
All other sites %
26% Lung & bronchus
15% Breast
10% Colon & rectum
6% Pancreas
6% Ovary
4% Leukemia
3% Non-Hodgkin lymphoma
3% Uterine corpus
2% Multiple myeloma
2% Brain/ONS
23% All other sites
ONS=Other nervous system.
Source: American Cancer Society, 2006.

5. What is cancer? Abnormal cell growth (neoplasia)‏
Malignant as opposed to benign
Benign: slow growth, non-invasive, no metastasis
Malignant: rapid growth, invasive, potential for metastasis

6. Phenotype of a cancer cell
The Six Hallmarks of Cancer
Self-sufficient growth signals
Constitutively activated growth factor signalling
Resistance to anti-growth signals
Inactivated cell cycle checkpoint
Immortality
Inactivated cell death pathway

7. Phenotype of a cancer cell (cont'd)‏
The Six Hallmarks of Cancer
Resistance to cell death
Activated anti- cell death signalling
Sustained angiogenesis
Activated VEGF signalling
Invasion and metastasis
Loss of cell-to-cell interactions, etc.

8. Is cancer a heritable disease?
There are heritable cancer syndromes
The majority of cancers, however, are not familial
Cancer is a genetic disease, but the majority of mutations that lead to cancer are somatic

9. What causes the mutations that lead to cancer?
Viruses: HPV --> cervical cancer
Bacteria: H. pylori --> gastric cancer
Chemicals --> B[a]P --> lung cancer
a component of cigarette smoke benzo[a]pyrene (BaP)
UV and ionizing radiation --> skin cancer
What do these agents have in common?

10. Mutagens Viruses: insertional mutagenesis Chemicals: DNA adducts
UV and ionizing radiation: single and double strand DNA breaks

11. What types of genes get mutated in cancer?
Oncogenes are activated
Normal function: cell growth, gene transcription
Tumor suppressor genes are inactivated
Normal function: DNA repair, cell cycle control, cell death

12. Smoking and Cancer
About one-third of all cancer cases in the United States are directly attributable to cigarette smoking.
Smoke contains many mutagenic chemicals, and places them in direct contact with lung tissues.
damages genes of epithelial cells lining the lungs

13. Tobacco Reduces Life Expectancy

14. Tumor suppressors “Guardian(s) of the genome”
Often involved in maintaining genomic integrity (DNA repair, chromosome segregation)‏
Mutations in tumor suppressor genes lead to the “mutator phenotype”—mutation rates increase
Often the 1st mutation in a developing cancer

15. p53—a classic tumor suppressor
“The guardian of the genome”
Senses genomic damage
Halts the cell cycle and initiates DNA repair
If the DNA is irreparable, p53 will initiate the cell death process

16. Rb—a classic tumor suppressor
Rb binds to a protein called E2F1
E2F1 initiates the G1/S cell cycle transition
When bound to Rb, E2F1 can't function
Thus, Rb is a crucial cell cycle checkpoint

17. Chromosomal Instability

18. Tumor-Suppressor Genes
Tumor suppressor genes encode proteins that turn off cell division in healthy cells.
Cancer may be initiated by the inappropriate activation of proteins that regulate the cell cycle, or by the inactivation of proteins that normally suppress cell division.

19. Cancer and the Cell Cycle
Cells control proliferation at several checkpoints.
All these controls must be inactivated for cancer to be initiated.
Induction of most cancers involves mutations of several genes.
explains why most cancers occur in people over 40
more time for individual cells to accumulate multiple mutations

20. The Cell Cycle and Cancer

21. Cancer Cancer is a growth disorder of cells.
uncontrolled and invasive growth
results in tumor
may metastasize
can be caused by mutagenic chemicals or possibly viruses
cell division never stops in a cancerous line, and are thus essentially immortal

22. Causes of Cancer Sarcomas - arise in connective tissue or muscle
Carcinomas - arise in epithelial tissue
Carcinogens are agents thought to cause cancer.
Ames test
Carcinogenic chemicals are all mutagenic.

23. The Stages of the Cell Cycle
1. Click on picture for cell cycle animation –
will go to
2. Use alt-tab keys to go between website
and power point presentation.
3. Click on blank space to proceed to next slide.)

24. Cancer and the Cell Cycle
Oncogenes - genes that when introduced into normal cells cause them to become cancerous
Originally discovered by transfection - nuclear DNA from tumor cells is isolated and cleaved into random fragments, and tested for ability to induce cancer

25. Cancer and the Cell Cycle
Proto-oncogenes are genes encoding proteins that stimulate cell division.
Mutated proto-oncogenes become cancer-causing genes (oncogenes).
Mutated alleles of many oncogenes are genetically dominant.

26. There are several factors that regulate the cell cycle and assure a cell divides correctly.
1.Before a cell divides, the DNA is checked to make sure it has replicated correctly. (If DNA does not copy itself correctly, a gene mutation occurs.
DNA replication animation:click on DNA picture

27. 2. Chemical Signals tell a cell when to start and stop dividing.
(Target cells animation: click on go sign)

28. Neighboring cells communicate with dividing cells to regulate their growth also.
(Normal contact inhibition animation: click on petri dish)

29. Cancer is a disease of the cell cycle
Cancer is a disease of the cell cycle. Some of the body’s cells divide uncontrollably and tumors form.
Tumors in Liver
Tumor in Colon

30. DNA mutations disrupt the cell cycle.
Mutations may be caused by:
1. radiation
2. smoking
3. Pollutants
4. chemicals
5. viruses

31. While normal cells will stop dividing if there is a mutation in the DNA, cancer cells will continue to divide with mutation.

32. Due to DNA mutations, cancer cells ignore the chemical signals that start and stop the cell cycle.
2 animations of cancer cells dividing: click on picture

33. Due to DNA mutations, cancer cells cannot communicate with neighboring cells. Cells continue to grow and form tumors.
Skin cancer
(cancer cells dividing: click on picture.)

34. SUMMARY Normal Cell Division DNA is replicated properly.
2. Chemical signals start and stop the cell cycle.
3. Cells communicate with each other so they don’t become overcrowded.
Cancer Cells
Mutations occur in the DNA when it is replicated.
2. Chemical signals that start and stop the cell cycle are ignored.
3. Cells do not communicate with each other and tumors form.

35. What can cancer therapies target?
Classic cancer therapies target rapidly dividing cells
Target the DNA
Ionizing radiation
Chemotherapy
Many side effects
Hair loss
Weakened immune system
Problems with GI tract

36. What can cancer therapies target?
Cancer treatments include drugs that can stop cancer cells from dividing.

37. What can cancer therapies target?
A person's immune system will not target tumor cells because they appear to be “self”
Some new therapies focus on activating one's immune system against a cancer

38. What can cancer therapies target?
Modern, targeted therapies attack specific proteins that are abnormally expressed in a tumor
May block over-expressed growth factor receptors --> Herceptin
Generally, there are few side effects since these therapies are specifically targeted to cancer cells

39. Curing Cancer Preventing start of cancer receiving signal to divide
mutations that increase number of receptors on cell surface amplify the division signal
relay switch
passage of signal into the cell’s interior
relay switch stuck in “ON” position

40. Curing Cancer amplifying the signal releasing the brake
amplification of signal within cytoplasm
releasing the brake
used to restrain cell division
checking readiness
ensures DNA is undamaged and ready to divide
stepping on the gas
restore telomerase inhibitor

41. Potential Cancer Therapy Targets

42. Curing Cancer Preventing the spread of cancer tumor growth metastasis
angiogenesis inhibitors
metastasis
cells break off and migrate