Biology of Cancer 134 , lecture 1

1. WHAT IS CANCER AND HOW DOES IT AFFECT
THE HUMAN CONDITION ?
Karobi Moitra (Ph.D)
NCI Frederick , NIH
Cancer Inflammation Program
Human Genetics Section
Frederick MD.

2. Is cancer a single disease
or
a group of diseases ?

3. Cancer is a group of related diseases which are
characterized by uncontrolled cellular growth
and division

4. Earliest signs of cancer : 3000 BC

5. Origin of the word “Cancer”
The origin of the word cancer is credited to the Greek physician Hippocrates
(460–370 B.C.), considered the "Father of Medicine." Hippocrates used the
terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming
tumors. In Greek, these words refer to a crab, most likely applied to the
disease because the finger-like spreading projections from a cancer called to
mind the shape of a crab.
The Roman physician, Celsus (28-50 B.C.), later translated the Greek term
into cancer, the Latin word for crab.
Galen (130-200 A.D.), another Roman physician, used the word oncos (Greek
for swelling) to describe tumors. Galen's term is now used as a part of the
name for cancer specialists -- oncologists.

6. Cancer is associated with abnormal cellular
proliferation
Cells divide when they should not divide and they
lack the normal control systems to shut off unwanted
cell division

7. Loss of Normal Growth Control
Normal
cell division
Cell Suicide or Apoptosis
Cell damage—
no repair
Cancer
cell division
First Second Third Fourth or
mutation mutation mutation later mutation R
Uncontrolled growth

8. In most cases to form a contiguous cell mass
called a tumor
R

9. Example of Normal Growth
Dead cells
shed from
outer surface
Epidermis
Cell migration
Dividing cells
in basal layer
Dermis
Each time one of these basal cells divides, it produces two cells. One remains in the basal layer and
retains the capacity to divide. The other migrates out of the basal layer and loses the capacity to
divide. The number of dividing cells in the basal layer, therefore, stays the same. R

10. The Beginning of Cancerous Growth
During the development of skin cancer, the normal balance between cell division and cell loss is disrupted.
The basal cells now divide faster than is needed to replenish the cells being shed from the surface of the
skin. Each time one of these basal cells divides, the two newly formed cells will often retain the capacity to R
divide, thereby leading to an increase in the total number of dividing cells.

11. Cell death =
Cell growth
Cell death <
Cell growth
R

12. Tumors (Neoplasms)
Underlying tissue
R
This gradual increase in the number of dividing cells creates a growing mass of tissue called a “tumor” or “neoplasm.”

13. Melanoma
R

14. Types of cancer / precancerous subtypes:
According to growth type:
Neoplasia - growth of cells to form a new structure eg: a tumor
Hyperplasia - excessive no. of cells.
Dysplasia - loss of normal arrangement of tissue (precancerous)
Carcinoma-in-situ - uncontrolled growth of cells that remains
at the same place (non-invasive).
Invasive carcinoma - can invade surrounding tissue and also
undergo metastasis. R

15. Hyperplasia
Excessive growth
Normal Hyperplasia
R

16. Dysplasia
Excessive growth Loss of cellular structure
& tissue arrangement
Normal Hyperplasia Mild dysplasia
R

17. Normal to Invasive
Excessive growth Loss of cellular structure Excessive growth Invades
& tissue arrangement in place
Normal Hyperplasia Mild Carcinoma in
dysplasia situ (severe
dysplasia) Cancer
(invasive)
R

18. Types of cancer / precancerous subtypes:
According to growth type:
Neoplasia - growth of cells to form a new structure eg: a tumor
Hyperplasia - excessive no. of cells.
Dysplasia - loss of normal arrangement of tissue (precancerous)
Carcinoma-in-situ - uncontrolled growth of cells that remains
at the same place (non-invasive).
Invasive carcinoma - can invade surrounding tissue and also
undergo metastasis. R

19. According to tissue type affected :
Carcinoma - tumors made up of principally epithelial cells
(cells that line inner and outer surfaces).
eg: cervical and skin cancers.
Sarcoma - made up principally of connective tissue cells
(cartilage, bone etc.)
eg: osteosarcoma.
Leukemia - Neoplastic growth of leucocytes (WBC) .
Lymphoma - excessive production of lymphocytes by lymph
nodes and spleen.
eg: Hodgkins disease. R

20. Different Kinds of Cancer
Leukemias:
Some common
carcinomas: Bloodstream
Lung Lymphomas:
Lymph nodes
Breast (women)
Colon
Some common
Bladder sarcomas:
Prostate (men) Fat
Bone
Muscle R

21. According to tissue type affected :
Carcinoma - tumors made up of principally epithelial cells
(cells that line inner and outer surfaces).
eg: cervical and skin cancers.
Sarcoma - made up principally of connective tissue cells
(cartilage, bone etc.)
eg: osteosarcoma.
Leukemia - Neoplastic growth of leucocytes (WBC) .
Lymphoma - excessive production of lymphocytes by lymph
nodes and spleen.
eg: Hodgkins disease. R

22. According to metastasis (invading capacity)
Benign tumor - these tumors have restricted growth and tend
to remain localized.
eg: wart.
Malignant tumor - these tumors do not remain localized but
invade other tissue and give rise to
secondary tumors in other parts of the
body (metastasis).
R

23. Malignant versus Benign Tumors
Benign (not cancer) Malignant (cancer)
tumor cells grow cells invade
only locally and cannot neighboring tissues,
spread by invasion or enter blood vessels,
metastasis and metastasize to
different sites
Time
R

24. Invasion and Metastasis
1
Cancer cells invade
surrounding tissues
and blood vessels
2
Cancer cells are
transported by the
circulatory system
to distant sites
3
Cancer cells
reinvade and grow
at new location
R

25. Different kinds According to growth type:
of cancer Neoplasia - growth of cells to form a new structure eg: a tumor
Hyperplasia - excessive no. of cells.
Dysplasia - loss of normal arrangement of tissue (precancerous)
Carcinoma-in-situ - uncontrolled growth of cells that remains
at the same place (non-invasive).
Invasive carcinoma - can invade surrounding tissue and also
undergo metastasis.
According to tissue type affected : According to metastasis (invading capacity)
Carcinoma - tumors made up of principally epithelial cells Benign tumor - these tumors have restricted growth and tend
(cells that line inner and outer surfaces). to remain localized.
eg: cervical and skin cancers. eg: wart.
Sarcoma - made up principally of connective tissue cells
(cartilage, bone etc.)
eg: osteosarcoma. Malignant tumor - these tumors do not remain localized but
invade other tissue and give rise to
secondary tumors in other parts of the
Leukemia - Neoplastic growth of leucocytes (WBC) .
body (metastasis).
Lymphoma - excessive production of lymphocytes by lymph
nodes and spleen.
eg: Hodgkins disease.
R

26. Why Cancer Is Potentially Dangerous
Brain
Melanoma
cells travel
through
bloodstream
Liver
Melanoma
(initial tumor)
R

27. If left untreated cancer can result in death……..
R

28. Naming Cancers
Cancer Prefixes Point to Location
Prefix Meaning
adeno- gland
chondro- cartilage
erythro- red blood cell
hemangio- blood vessels
hepato- liver
lipo- fat
lympho- lymphocyte
melano- pigment cell
myelo- bone marrow
myo- muscle
osteo- bone R

29. Microscopic Appearance of Cancer Cells
R

30. Normal cell Cancer cell
R

31. Characteristic adaptive features of cancer cells :
1. Loss of contact inhibition
Normal cells stop growing when their plasma membranes
come into contact with one another - normal cells stop
moving when they contact each other this is called
contact inhibition, cancer cells lose the property of
contact inhibition. Transformed cells do not stop dividing
after forming a monolayer division continues until several
layers of cells are formed.
R

32. 2. Unrestrained control of growth
Cancer cells lack the normal control systems to shut
off unwanted growth.
3. Metastasis
Metastasis is the spread of cancer cells from a primary
site of origin to other tissues where they grow as
secondary tumors.
R

33. Some biochemical properties of cancer cells :
1. Increased glycolysis (Warburg effect)
Otto Warburg observed that virtually every type of cancer
cells that form solid tumors excrete much larger quantities of
lactic acid than its normal counterpart. This is known as the
‘Warburg effect’.
Unlike normal cells, which break down sugar using oxidative
pathways (or the Krebs cycle), tumor cells used non-
oxidative pathways (glycolysis) to generate energy from
sugar.
R

34. 2. Alterations in cytoskeletal proteins
Less organized/ disorganized arrangement of
cytoskeletal proteins - such as myosin , tubulin etc.
R

35. 3. Loss of anchorage dependence
Cancer cells in culture can grow suspended in
media while most normal cells need to attach to a
substratum to grow (anchored).
R

36. 4. Cancer cells are seemingly immortal
Cancer cells in culture can continue to grow indefinitely.
R

37. The Somatic Mutation Theory
Of Cancer
Theodore Boveri 1914
He stated that the fundamental
cause of cancer was in chromatin
imbalance in the cells from which
cancer arises.
Evidence : Many cancers have
chromosomal abnormalities
R

38. R

39. The cell cycle R

40. R

41. R

42. R

43. What Causes Cancer?
R

44. What Causes Cancer?
Some viruses or bacteria
Some chemicals Radiation
Heredity
Diet
Hormones
R

45. Population-Based Studies
Regions of Highest Incidence
U.K.:
Lung
cancer
JAPAN:
Stomach CANADA:
cancer Leukemia
U.S.:
CHINA: Colon
Liver cancer
cancer BRAZIL:
AUSTRALIA: Cervical
Skin cancer
cancer
A striking finding to emerge from population studies is that cancers arise with different frequencies
in different areas of the world. For example, stomach cancer is especially frequent in Japan, colon
cancer is prominent in the United States, and skin cancer is common in Australia. What is the R
reason for the high rates of specific kinds of cancer in certain countries?

46. Heredity? Behaviors? Other Factors?
Colon Cancer Stomach Cancer
(Number of new cases (Number of new cases
per 100,000 people) per 100,000 people)
100 100
70
50
5 7
0 Japan Japanese U.S. 0 Japan Japanese U.S.
families families
in U.S. in U.S.
In theory, differences in heredity or environmental risk factors might be responsible for the different cancer
rates observed in different countries. Studies on people who have moved from one country to another
suggest that exposure to risk factors for cancer varies by geographic location. For example, in Japan, the
rate of colon cancer is lower, and the rate of stomach cancer is higher, than in the United States. But this
difference has been found to gradually disappear in Japanese families that have moved to the United States.
This suggests that the risk of developing the two kinds of cancer is not determined primarily by heredity. The R
change in risk for cancer for Japanese families could involve cultural, behavioral, or environmental factors
predominant in one location and not in the other.

47. Tobacco Use and Cancer
Some Cancer-Causing Chemicals in Tobacco Smoke
R

48. Low-Strength Radiation
High
Dallas
Skin
Cancer
Incidence Pittsburgh
Detroit
Low
Least Most
Annual Sunshine
(UV radiation)
Some atoms give off radiation, which is energy that travels through space. Prolonged or repeated
exposure to certain types of radiation can cause cancer. Cancer caused by the sun’s ultraviolet
radiation is most common in people who spend long hours in strong sunlight. Ultraviolet radiation
from sunlight is a low-strength type of radiation. Effective ways to protect against ultraviolet radiation
and to prevent skin cancer are to avoid going into strong, direct sunlight and to wear protective
clothing. Sunscreen lotions reduce the risk of some forms of skin cancers. R

49. High-Strength Radiation
High
Leukemia
Incidence
Low
Least Most
X-ray Dose
(atomic radiation)
Increased rates of cancer also have been detected in people exposed to high-strength forms of radiation such as
X-rays or radiation emitted from unstable atoms called radioisotopes. Because these two types of radiation are
stronger than ultraviolet radiation, they can penetrate through clothing and skin into the body. Therefore, high-
strength radiation can cause cancers of internal body tissues. Examples include cancer caused by nuclear fallout
R
from atomic explosions and cancers caused by excessive exposure to radioactive chemicals.

50. Lag Time
20-Year Lag Time Between
Smoking and Lung Cancer
Cigarette
consumption
(men)
4000
Lung
150
Cigarettes 3000 cancer
Smoked (men) Lung Cancer
per Person 100 Deaths (per
per Year 100,000 people)
2000
50
1000
1900 1920 1940 1960 1980
Year
Chemicals and radiation that are capable of triggering the development of cancer are called “carcinogens.” Carcinogens act through a
multistep process that initiates a series of genetic alterations (“mutations”) and stimulates cells to proliferate. A prolonged period of time is
usually required for these multiple steps. There can be a delay of several decades between exposure to a carcinogen and the onset of R
cancer. For example, young people exposed to carcinogens from smoking cigarettes generally do not develop cancer for 20 to 30 years.
This period between exposure and onset of disease is the lag time.

51. Viruses
Virus inserts
and changes
genes for
cell growth
Cancer-linked virus
R

52. Examples of Human Cancer Viruses
Some Viruses Associated with Human Cancers
R

53. Bacteria and Stomach Cancer
Patient’s H. pylori
tissue
sample
The bacterium Helicobacter pylori, which can cause stomach ulcers, has been associated with the
development of cancer, so people infected with H. pylori are at increased risk for stomach cancer.
Research is under way to define the genetic interactions between this infectious agent and its host
tissues that may explain why cancer develops. R

54. Heredity and Cancer
All Breast Cancer Patients
Inherited factor(s)
Other factor(s)
Cancer is not considered an inherited illness because most cases of cancer, perhaps 80 to 90 percent, occur in people
with no family history of the disease. However, a person’s chances of developing cancer can be influenced by the
inheritance of certain kinds of genetic alterations. These alterations tend to increase an individual’s susceptibility to
developing cancer in the future. For example, about 5 percent of breast cancers are thought to be due to inheritance of
particular form(s) of a “breast cancer susceptibility gene.”
R

55. Heredity Can Affect Many Types of Cancer
Inherited Conditions That Increase Risk for Cancer
Inherited mutations can influence a person’s risk of developing many types of cancer in
addition to breast cancer. For example, certain inherited mutations have been described
that increase a person’s risk of developing colon, kidney, bone, skin or other specific forms
of cancer. But these hereditary conditions are thought to be involved in only 10 percent or
fewer of all cancer cases.
R

56. Cancer is a group of related diseases which are
characterized by uncontrolled cellular growth
and division
Cells divide when they should not divide and they
lack the normal control systems to shut off unwanted
cell division
R

57. How does cancer affect the
human condition ?

65. CARCINOMA !!!

66. ----------------------
E R
N C
C A

67. "He who cures a disease may
be the skill fullest, but he that
prevents it is the safest
physician”
Thomas Fuller