Cancer Fundamentals

Julie Randolph-Habecker, Ph.D.Director, Experimental

Histopathology Shared Resource

Cancer Overview

Leading cause of death in US1.2 million diagnosed each year

More common after age 50Lifestyle changes can cut the cancer rate by 60%

Not smoking, eating healthy diet, exercising moderately

60% of people with cancer now live longer than 5 years

Cancer incidence and mortality in the USA for the year 2000.

Cancer Incidence as a function of age.The number of newly diagnosed cases of colon cancer in woman in England and Wales in one year is plotted as a function of age at diagnosis.

Cancer

Group of related diseasesAbnormal growth of cellsRare event – 30 trillion cellsOne renegade cell forms tumorWhen they spread – MetastasisCures – one shoe does not fit all

Causes of Cancer

Smoking contribute to up to 30% of cancer deaths

Tobacco smoke is the most lethal carcinogen in North America

Diet accounts for about 30% of cancer deaths

Saturated fats High salt intake Alcohol consumption

Causes of Cancer

Pathogens account for about 15% of cancer deaths

HPV and cervical cancerHHV8 and Kaposi's SarcomaHepatitis B and C and liver cancerEpstein-Barr Virus and Burkitt’s LymphomaHelicobacter pylori is likely associated with stomach cancer

PapillomavirusDNA-based virusesInfect skin and mucous membranesInfect humans and other animalsOver 100 human types

Causes of Cancer

RadiationEnvironmental and Occupational Chemicals

Years after exposure to 2-naphthylamine

Causes of Cancer

Hereditary FactorsSteroid HormonesPopulation Demographics

http://www.yourdiseaserisk.wustl.edu/

Benign versus malignant tumors (“Good” versus “Evil”); the diagram illustrates types that might be found in the breast

Benign Tumors

Leiomyoma or uterine fibroid

Meningioma

Types of CancerCancers are named according to types of tissue it originated in, and what type of cell it started in

e.g., ductal breast carcinomaCarcinoma: cancer of the skin and inner membranes in the body (lungs, stomach, intestines)

Accounts for 90% of human cancersSarcoma: cancer of tissue that support and connect parts of the body (muscle, bone, cartilage, and fat)

Accounts for less than 2% of human cancerLeukemia and lymphomas: cancer of the blood-forming tissues

Accounts for about 8% of human cancer

Names of TumorsTissue Cell Type Benign tumor Malignant tumor

Solid epitheila organs:liver, kidney, prostrate, thyriod, pancreas, pituitary, etc.

Specific epithelium Adenoma Carcinoma

Skin Squamous epitheliumBasal cellPigment cell

Papilloma

Melanoma

Squamous carcinomaBasal cell carcinomaMalignant melanoma

Mesenchyme:Fibrous tissueFatBoneCartilageSmooth muscleStriated MuscleBlood vesselsLymph nodes

FibrocytesAdipocytesOsteocytesChondrocytesSmooth muscle cellsMuscle cellsEndotheliumEndothelium

FibromaLipomaOsteomaChondromaLeiomyomaRhabdomyomaHeamangiomaLymphangioma

FibrosarcomaLiposarcomaOsteosarcomaChondrosarcomaLeiomyosarcomaRhabdosarcomaHeamangiosarcomaLymphoangiosarcoma

Reticuloendothelial:White blood cells

Red blood cellsLymph nodes

Myeloid cellsLymphocytesErythrocytes

Myeloid leukemiaLympho leukemiaErythroleukaemiaNon-Hodgkin’s lymphomaHodgkin’s disease

Osteosarcoma of bone

Hepatic Adenoma

Squamous Cell Carcinoma of lung

Biology of Cancer

Basement membrane

INITIATIONChemicals, radiation, viruses

PROMOTIONExposure to carcinogens

Small benign tumor or mild dysplasia

DEVELOPMENT OF THE MALIGNANT PHENOTYPEPreinvasive lesion Increasing dysplasia

Primary malignant tumor (carcinoma)

METASTASIS

Vessel

Normal colon cell

Increase cell

growthAdenoma

IAdenoma

IIAdenoma

IIICarcinoma Metastasis

Mutation of APC on

Chromosome 5

DNA loses methyl group

K-RAS gene

mutation

Loss of DCC on

Chromosome 18

p53 mutations

Chromosome 17 loss

Other genetic

changes

Genetic changes and progression in colon cancer

Early warning signs of cancer

Changes in bowel or bladder habitsA sore that does not healUnusual bleeding or dischargeThickening or a lump in the breast or any other part of the bodyIndigestion or difficulty swallowingChange in appearance of a wart or moleA nagging cough or hoarseness

FE

D

CBA

Screening ToolsEndoscopy

A thin lighted tube used to look inside body cavities (esophagus, stomach, colon, intestine)

Pap smear for cervical cancerFecal occult blood test for colon cancerBlood test to look at red and white blood cell countsProstate specific antigen (PSA) for prostate cancerX-ray (mammogram), Ultrasound, CT scan, and MRI scanCytogenetics

Karyotyping

Chronic Myelogenous Leukemia (CML)

46,Y,der(Xq?)?inv(X)add(X),t(1;7)(p36.1;p11.2),del(3)(q23q25),del(5)(q13q33),?inv(8),der(9)add(9)(p11)add(9)q22), del(11)(q13),del(12p11.2p13),-19

Tumor StagingStaging is key factor in determining treatment and prognosisMost common system: TNM = Tumor, Lymph Node, Metastasis

T = size of tumor (0 to 3)N = extent of spread to lymph nodes (0 to 3)M = extent of spread throughout body (0 to 3)

Example: T-1, N-0, M-0Stage 1 tumor: tumor is 2 cm or less and has not spread to nearby lymph nodes or metastasizedPrognosis is excellent

Example: T-3, N-1, M-0Stage 3 tumor: tumor is greater than 5 cm and has spread to nearby lymph nodes, but no evidence of spread to distant tissuePrognosis is mixed

Stage 4 tumor = M-1Metastasis is widespread and prognosis is poor

Tumor Staging

Staging is key factor in determining treatment and prognosisMost common system: TNM = Tumor, Lymph Node, Metastasis

T = size of tumor (0 to 3)N = extent of spread to lymph nodes (0 to 3)M = extent of spread throughout body (0 to 3)

Tumor Grade

Based upon microscopic appearance of a tumorA well-differentiated tumor is composed of cells that closely resemble the cell of originPoorly differentiated tumors have cells that are difficult to recognize as to their cell of origin

Associated with poor outcomeMost grading systems have three or four grades (designated with numbers or roman numerals).

Gleason’s Pattern

Well Differentiated

Moderately Differentiated

Poorly Differentiated

Other Factors

Treatment

SurgeryEffective and fast

Radiation therapyFocused radiation on tumor to cause genetic damage with the goal to kill cellsTargets rapidly dividing cells

ChemotherapyUses anticancer drugs to treat the whole bodySometimes used in combination with radiation therapy (e.g., breast, lung, colon, prostate)

Treatment

Hormone therapyPrevent cancer cells from using or receiving the hormones they need to grow/survivee.g., tamoxifen and raloxifene are antiestrogen drugs

Treatment

Biological therapyImmunotherapy

Uses body’s immune system to eliminate cancer cellsUses antibodies to direct attack the tumor or to deliver toxic agents

Herceptin is an antibody that targets cells that overproduce HER-2

Bone marrow transplantation

How does cancer kill

Multisystem organ failureInfection

32-47%Hemorrhage & Thromboembolism

10-20%Cachexia

>1%

Areas of Cancer Research

PreventionNutritionTobacco

DetectionEarly Detection and Intervention

TreatmentEnvironmental Carcinogenesis/ toxicologyCauses/etiology

Early Detection and Intervention

Using models of cancerAnalyzing samples with ProteomicsIdentify small molecules associated with cancerTest on archived patient samplesDevelop screening tools for early detection

Sensitive and specificNon-invasive

Research for Understanding

YeastLed to an understanding of how the control of cell division

ChemistryLipid chemistry to develop drugs

VirusesResearch on chicken virus helped identify oncogenes

Clinical trials

Research studies in which new treatments (e.g., drugs, diagnostic procedure, vaccines) are tested in people to see if they are safe and effectiveAll new treatments must go through clinical trials

Future Research Directions

Better detection/diagnosisTarget vasculaturePrevent metastasesGene therapy

Copyright ©2007 American Association for Cancer Research

Veiseh, M. et al. Cancer Res 2007;67:6882-6888

Questions?

Thanks:

Karen Peterson

Michele Talquist

Eileen Bryant

Jim Olson