1. Cancer

2. Learning Objectives The students will be able to:
Identify the 3 most prevalent cancers for a person of their gender
Define cancer
Explain why cancer is a genetic disease even though its heritability is rather low
Compare the functions of oncogenes and tumor suppressor genes
Explain why tumor suppressors are often the 1st genes mutated in a developing cancer
List the Six Hallmarks of Cancer
Describe the advantages of using modern, targeted cancer therapies

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

4. 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.

5. 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.

6. Cancer
Cancer is one of the most common diseases in the developed world:
1 in 4 deaths are due to cancer
1 in 17 deaths are due to lung cancer
Prostate cancer is the most common cancer in men
Breast cancer is the most common cancer in women
There are over 100 different forms of cancer
What is cancer video

7. Terminology
A factor which brings about a mutation is called a mutagen.
A mutagen is mutagenic.
Any agent that causes cancer is called a carcinogen and is described as carcinogenic.
So some mutagens are carcinogenic.

8. Carcinogens Ionising radiation – X Rays, UV light
Chemicals – tar from cigarettes
Virus infection – papilloma virus can be responsible for cervical cancer.
Hereditary predisposition – Some families are more susceptible to getting certain cancers. Remember you can’t inherit cancer its just that you maybe more susceptible to getting it.

9. 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

10. What causes the mutations that lead to cancer?
Viruses: HPV --> cervical cancer
Bacteria: H. pylori --> gastric cancer
Chemicals --> Chemical in tar--> lung cancer
UV and ionizing radiation --> skin cancer
What do these agents have in common?

11. Mutagens Viruses: insertional mutagenesis
Chemicals: DNA adducts (a segment of DNA bound to a cancer causing chemical)
UV and ionizing radiation: single and double strand DNA breaks

12. 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

13. 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

14. p53—a classic tumor suppressor
Senses genomic damage
Halts the cell cycle and initiates DNA repair
If the DNA is irreparable, p53 will initiate the cell death process

15. 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

16. HER2/neu—an oncogene A growth factor receptor
25-30% of breast cancers over-express HER2/neu
Which hallmark of cancer does this lead to?
Herceptin is used as a treatment

17. 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

18. Phenotype of a cancer cell (cont'd)‏
The Six Hallmarks of Cancer
Resistance to cell death (apoptosis: programed cell death)
Activated anti- cell death signalling
Sustained angiogenesis
Activated Blood vessel formation
Invasion and metastasis
Loss of cell-to-cell interactions, etc.

19. The Development of Cancer
Within every nucleus of every one of the human body's 30 trillion cells exists DNA, the substance that contains the information needed to make and control every cell within the body. Here is a close-up view of a tiny fragment of DNA.

20. 1. DNA of a normal cell
This piece of DNA is an exact copy of the DNA from which it came. When the parent cell divided to create two cells, the cell's DNA also divided, creating two identical copies of the original DNA.

21. 2. Mutation of DNA Change in the sequence of DNA
This DNA has suffered a mutation, either through mis-copying (when its parent cell divided), or through the damaging effects of exposure to radiation or a chemical carcinogen.

22. 3. Genetically altered cell
Sometimes a genetic mutation will cause a cell and its descendants to reproduce even though replacement cells are not needed.

23. 4. Spread and second mutation
The genetically altered cells have, over time, reproduced unchecked, crowding out the surrounding normal cells.
After about a million divisions, there's a good chance that one of the new cells will have mutated further. This cell, now carrying two mutant genes, could have an altered appearance and be even more prone to reproduce unchecked.

24. 5. Third mutation
Over time and after many cell divisions, a third mutation may arise. If the mutation gives the cell some further advantage, that cell will grow more vigorously than its predecessors and thus speed up the growth of the tumour.

25. 6. Fourth mutation
The new type of cells grow rapidly, allowing for more opportunities for mutations. The next mutation paves the way for the development of an even more aggressive cancer.
At this point the tumour is still contained.

26. 7. Breaking through the membrane
The newer, wilder cells created by another mutation are able to push their way through the epithelial tissue's basement membrane, which is a meshwork of protein that normally creates a barrier. The invasive cells in this tumour are no longer contained.
At this point the cancer is still too small to be detected.

27. 8. Angiogenesis
Angiogenesis takes place. Angiogenesis is the recruitment of blood vessels from the network of neighbouring vessels.
With the new blood supply, however, the growth of the tumour accelerates; it soon contains thousand million cells and, now the size of a small grape, is large enough to be detected as a lump

28. 9.Invasion and dispersal
The tumour has now invaded the tissue beyond the basement membrane.

29. 10. Tumour cells travel - metastasis
What makes most tumours so lethal is their ability to metastasize -- that is, establish new tumour sites at other locations throughout the body forming secondary tumours. .

30. 11. Metastasis
To form a secondary tumour, a tumour cell needs to leave the vessel system and invade tissue. The cell must attach itself to a vessel's wall. Once this is done, it can work its way through the vessel and enter the tissue.

31. 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

32. 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

33. 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

34. Types Of Cancers Classification of cancers
Carcinomas : a cancer arising in the epithelial tissue of the skin or of the lining of the internal organs.
Sarcomas: a malignant tumor of connective or other non- epithelial tissue
Lymphomas: cancer of the lymph nodes
Leukemias: cancer of white blood cells

35. Colon And Rectal Cancers
Third most common cancer in men and women with over 148,610 new cases diagnosed in 2006
Risk factors: over 50 years old, obese, family history of colon or rectum cancer or polyps, diets high in fats, low in fiber, smoking, high alcohol consumption, lack of exercise
90% of colorectal cancers are preventable
Treatment: radiation, surgery, and possible chemotherapy
Prevention: regular exercise, a diet heavy in fruits and plant-origin foods, a health weight, and moderation in alcohol consumption

36. Prostate Cancer
Most common cancer in American men, excluding skin cancer
In 2006, 234,460 new cases diagnosed
1 in 3 men will be diagnosed in their lifetime
Prostate is a muscular, walnut-sized gland the surrounds part of the urethra. Its primary function is to produce seminal fluid.
Symptoms: nonspecific, weak or interrupted urine flow, difficulty starting or stopping urination
Risk factors: age, race, nationality, family history, diet, lifestyle, and vasectomy
Prevention: diet high in lycopenes, vitamin E

37. Skin Cancer
Long term effects of sun exposure can result in skin cancer
Malignant melanoma, deadliest form of skin cancer
Sun give off 3 types of harmful rays:
UVA
UVB
UVC
Prevention: limit exposure to harmful UV rays, drink more fluids than usual, apply cool compresses to skin, moisturize skin

38. Types of Ultraviolet Rays
Figure 16.7

39. Skin Cancer – cont. What to look for – The ABCD rule
Asymmetry – half of mole does not look like the other half
Border irregularity – the edges are uneven
Color – pigmentation is not uniform
Diameter – greater than 6mm

40. Testicular Cancer Affects nearly 8,250 young men in 2006
Men between the ages are at the greatest risk
Important to practice regular testicular self exams
Lance Armstrong Foundation “LiveStrong” campaign to raise awareness

41. Ovarian Cancer
Fifth leading cause of cancer death for women, 20,180 new cases diagnosed reported in 2006
Most common symptom is enlargement of the abdomen
Risk factors include: family history, age, childbearing, cancer history, fertility drugs, talc use in genital area, genetic predisposition
Prevention: diet high in vegetables and low in fat, exercise, sleep, stress management, and weight control

42. Cervical and Endometrial (Uterine) Cancer
9,710 new cases of cervical cancer, 41,200 cases of endometrial cancer in U.S. in 2006
Pap test – cells are taken from the cervical region
Risk factors:
Cervical cancer: early age at first intercourse, multiple sex partners, cigarette smoking
Endometrial cancer: age, endometrial hyperplasia, overweight, diabetes, and high blood pressure

43. Other Cancers Pancreatic cancer – “silent” 4% 5-year survival rate
Leukemia – cancer of blood forming tissues

44. Detecting Cancer
The earlier the diagnosis the better the prospect for survival
Magnetic resonance imaging (MRI)
Computerized axial tomography scan (CAT scan)
Prostatic ultrasound
Regular self-exams, and check ups

45. New Hope In Cancer Treatments
Remove less surrounding tissue during surgery
Combine surgery with radiation or chemotherapy
Immunotherapy
Cancer-fighting vaccines
Gene therapy
Stem cell research