CANCER

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CANCER
Nomenclature and Classifications
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NOMENCLATURE

• Neoplasm
• an abnormal mass of tissue, the growth of which
  exceeds and is uncoordinated with the normal
  tissues and which persists in the same excessive
  manner after the cessation of the stimuli which
  evoked the change.
• Sir Rupert Willis

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NOMENCLATURE

• Benign Add oma to cell of origin
• Adenoma
• Fibroma
• Osteoma
• Fibroadenoma

• Malignant
• Sarcoma mesenchymal
• Fibrosarcoma
• Osteosarcoma
• Carcinoma epithelial
• adenocarcinoma
• squamous cell carcinoma
• Melanoma
• Seminoma
• Teratoma

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Categories of Cancers
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Colorectal Tumors
Familial Adenomatous Polyposis
Hereditary Nonpolyposis Colorectal Cancer
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Lung Cancer Autopsy
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Expression-Based Tumor Classification Scheme
Genes Distinguishing ALL from AML. Expression
pattern of 50 human genes most highly correlated
with ALL-AML class distinction.
Expression Pattern Greater than the mean
Expression Pattern Lower than the mean
Golub et al., 1999
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Expression-Based Tumor Classification Scheme
Breast Cancer Classification by Microarray
Analysis Yields Distinct Subcategories of Tumor
Types
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Expression-Based Tumor Classification Scheme
With Related Tumors Exhibiting Similar Expression
Profiles
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Expression-Based Tumor Classification Scheme
With Prognostic Value for Clinical Outcome
Kaplan-Meier curves for survival (A) and freedom
from symptoms (B) of the cohort of patients
classified in the previous slide
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CANCER
Epidemiology Prevalence, Trends and Contributing
Factors
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Leading Causes of Death in US 1973 vs 1997
1975
2000
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Mortality in Women as a Function of Age
Breast Cancer is the predominant cause of death
only in women between 35 and 55
Source NY Times Jan. 26, 1999
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Estimated U.S. Cancer Prevalence, 1/1/2000
Primary Site
Total
Male
Female
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Estimated New Cancer Cases and Deaths, 2003
in thousands
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Cancer Incidence and Mortality Rates - Females
Incidence
Mortality
Uterus Breast Pancreas Ovary Stomach Lung
Bronchus Colon Rectum
Breast Colon Rectum Lung Bronchus Uterine
Corpus Ovary Non-Hodgkins Lymphoma
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Cancer Incidence and Mortality Rates - Males
Incidence
Mortality
Pancreas Liver Prostate Stomach Lung
Bronchus Colon Rectum Leukemia
Prostate Colon Rectum Lung Bronchus Urinary
Bladder Non-Hodgkins Lymphoma Melanomas
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5-Year Relative Survival Rates, 1989-1995
White Patients
Black Patients
Percentage of patients alive 5 years after
being diagnosed for the indicated cancer
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Reduction in Childhood Leukemia Mortality
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Recent Trends in Cancer Rates

• Cancers on the Increase
• Lung Cancer and Smoking (females)
• Skin Melanoma and Sun Exposure
• Non-Hodgkins lymphomas and HIV
• Cancers on the Decrease
• Lung Cancer and Smoking (males)
• Prostate
• Breast
• Colon
• Stomach

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Regions of High and Low Incidence of Cancer
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The Effect of Migration on the Incidence of
Cancer
West Africa to the United States
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The Effect of Migration on the Incidence of
Cancer
Japan to Hawaii
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Cancer Incidence as a Function of Meat Consumption
Colon Cancer Annual Incidence in Women (per
100,000 women)
MB 523
Meat Consumption (gm/person/day)
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Lung Cancer Deaths Track Cigarette Consumption
5000
150
4000
)
)
3000
Cigarettes per adult per year
Lung Cancer Deaths/100,000/yr
100
(
2000
(
50
1000
1900
1920
1940
1960
1980
YEAR
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Breast Cancer Versus Age at First Childbirth
More Likely
Same at Childless Women
Relative Likelihood of Developing Breast Cancer
Less Likely
MB 523
Age at Birth of First Child
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CANCER
Molecular Basis of Cancer Gatekeepers and
Caretakers
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Cancer Death Rate as a Function of Age
Death Rate Increases with Age to the Fifth Order
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Acquired Capabilities of a Cancer Cell
Most cancer cells gain new potential in at least
six arenas, although by different mechanisms in
different cancers
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Stages of Cancer Development - Mutation
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Stages of Cancer Development - Hyperplasia
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Stages of Cancer Development - Dysplasia
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Stages of Cancer Development - In Situ Tumor
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Stages of Cancer Development - Metastasis and
Angiogenesis
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Cervical Dysplasias and Cancers as a Function of
Age
Most cervical dysplasias do not progress to
cancers
MB 523
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The Eukaryotic Cell Cycle
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The Eukaryotic Cell Cycle
G0
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The Eukaryotic Cell Cycle - Regulation

• Restriction Point
• Point of commitment in G1 at which cell attends
  to external signals
• Gatekeepers
• Proteins that regulate the entry into the cell
  cycle
• Caretakers
• Proteins that maintain the integrity of the
  genome and the proper order of the cell cycle
• Checkpoints
• Surveillance program for intrinsic and extrinsic
  regulation of the order and progression of the
  cell cycle

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Regulation of the Eukaryotic Cell Cycle
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Checkpoints - Intrinsic and Extrinsic Surveillance
b
c
Intrinsic mechanism
a
d
e
Extrinsic mechanism
Damage
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Checkpoints - Regulating Cell Cycle Progression
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Genetic Instabilities in Human Cancers

• Sequence Instabilities (NIN and MIN)
• Chromosome Number Changes (CIN)
• Chromosome Translocations
• Gene Amplifications

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Genetic Instabilities in Human Cancers
Many human tumor cells exhibit extensive
aneuploidy
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Genetic Instabilities in Human Cancers
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Recent History of Novel Therapeutic Approaches
Bad News

• Resistance to Gleevac (Abl kinase inhibitor)
• Poor performance of some EGF receptor inhibitors
• Ras inhibitors failed clinical trials

Good News

• Anti-VEGF antibody treatment extended median
  survival of colon cancer patients from 15.6 to
  20.3 mo.
• Immunotherapy finally showing promise
• Herceptin (anti Her2/Neu) extends survival
  following breast cancer metastasis by 20
• Some promising Phase III results with other EGF
  receptor inhibitors (Erbitux)
• Vaccine against HPV reduces cervical cancer risk