MOL523 The Molecular Basis of Cancer

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MOL523 The Molecular Basis of Cancer
Syllabus and Assignments
http//microarray.princeton.edu/mb523/mb523-2006/d
efault06.htm
or
www.molbio.princeton.edu Graduate
Program Courses MOL 523
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MOL523 The Molecular Basis of Cancer
Requirements
Read the assigned papers
Midterm paper Molecular basis of your favorite
cancer
Final oral presentation Propose a novel cure for
your favorite cancer
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CANCER
What is Cancer?
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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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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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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
2002
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Mortality in Women as a Function of Age
Breast Cancer is the predominant cause of death
in women only between 35 and 55
Source NY Times Jan. 26, 1999
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Cancer is the Leading Cause of Death in Most
Groups

• Cancer is the leading cause of death among
• Americans younger than 85 (476,009 in 2002)
• Women between 40 and 79
• Men between 60 and 79

• Estimates for 2005
• 1,372,910 new cases of cancer
• 570,280 deaths from cancer

Source NY Times, Feb 1, 2005
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Estimated U.S. Cancer Prevalence, 1/1/2000
Primary Site
Total
Male
Female
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Cancer Incidence by Site (US Males, 2002)
Cancer Deaths by Site (US Males, 2002)
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Cancer Incidence by Site (US Females, 2002)
Cancer Deaths by Site (US Females, 2002)
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Estimated New Cancer Cases and Deaths, 2005
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
100
1995-2001
1989-1995
80
White
Black
60
40
20
0
Lung
Liver
Testis
Brain
Colon
Breast
Ovary
Uterus
Cervix
Kidney
Kaposi
Larynx
Rectum
Urinary
Prostate
Thyroid
Hodgkin
Stomach
Myeloma
Pancreas
Leukemia
Melanoma
Oral Cavity
Non-Hodgkin
Mesothelioma
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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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Recent History of Novel Therapeutic Approaches
Bad News

• Resistance to Gleevac (Abl kinase inhibitor)
• 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 EGF receptor inhibitors (Erbitux, Iressa,
  Tarceva) approved for lung cancer treatment
• Vaccine against HPV reduces cervical cancer
  incidence
• Alimta approved for NSCLC and Mesothelioma