ONCOLOGY

Wh

at Is Can

cer?

CANCER DIAGNOSIS

• The term “Cancer” has been use todescribe over 100 different diseasescharacterized by uncontrolled cellgrowth

WARNINGS SIGNS

• Weight loss

• Persistent Fever

• Fatigue

• Sores

• Bowel patterns

• Pain

• Indigestion

• Lump

• Unusual bleeding

Different Kinds of Cancer

Some commoncarcinomas:

Lung

Breast (women)

Colon

BladderProstate (men)

Leukemias:Bloodstream

Lymphomas:Lymph nodes

Some commonsarcomas:Fat

Bone

Muscle

Artwork by Jeanne Kelly. © 2004.

Naming Cancers

Cancer Prefixes Point to LocationPrefix Meaning

adeno-

chondro-

erythro-

hemangio-

hepato-

lipo-

lympho-

melano-

myelo-

myo-

osteo-

gland -

cartilage -

red blood cell

blood vessels

liver -

fat-

lymphocyte

pigment cell

bone marrow

muscle -

bone -

Loss of Normal Growth Control

Normalcell division

Cell Suicide or Apoptosis

Cell damage-no repair

Cancercell division

First Secondmutation mutation

Third Fourth ormutation later mutation

Uncontrolled growth

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Malignant versus Benign Tumors

Benign (not cancer)tumor cells growonly locally and cannotspread by invasion ormetastasis

Malignant (cancer)cells invadeneighboring tissues,enter blood vessels,and metastasize todifferent sites

___ Jjaa

Time

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Why Cancer Is Potentially Dangerous

Brain

LiverMelanoma

(initial tumor)

Artwork by Jeanne Kelly. © 2004.

Melanomacells travelthroughbloodstream

PROPERTIES OF CANCER CELLS

* Growth without “go” (positive) signals

* Failure to respond to “stop” (negative) signals

* Evasion of programmed cell death (apoptosis)

* Unlimited cell division

* Sustained angiogenesis (stimulation of blood

vessel growth)

* Tissue invasion and metastasis

GROWTH WITHOUT “GO”(POSITIVE) SIGNALS

* Growth factors

* Oncogene

FAILURE TO RESPOND TO “STOP”(NEGATIVE) SIGNALS

• Contact inhibition

Tumour suppressor genes

EVASION OF PROGRAMMED CELLDEATH (APOPTOSIS)

• Death signals

p53

UNLIMITED CELL DIVISION

* Telomeres

Telomerases

SUSTAINED ANGIOGENESIS(STIMULATION OF BLOOD VESSEL

GROWTH)

• VEGF (Vascular Endothelial GrowthFactors)

Nutrient, oxygen

TISSUE INVASION AND METASTASIS

* 90% of cell death due to single cellmutation

Migration

COMMON DIAGNOSTIC TESTS

• Blood test

• Imaging test

• Biopsy

• Cancer Staging

BLOOD TESTS

• Tumour markers - protein that arefound to be elevated in certaincancer

Use to check for treatment response

BLOOD TESTS

* Examples includes:

* CA125 for Ovarian Cancer (protein produced

when abdominal tissues are inflamed)

* PSA also known as Prostate specific antigen for

Prostate cancer(protein produce by prostate

cells, when too many will increase)

* AFP also known as alpha fetoprotein for liver

cancer (protein produce by liver tumours but

also elevate in hepatitis)

IMAGING

• X rays, ultrasound to create image of

internal structures

• CT scan (multiple X rays to form 3D

image)

• MRI also known as magnetic resonance

imaging use magnetic field to create

image

BIOPSY

• Removal of small piece of tissue from

patient

* Expert to look at microscopic images,

check for tumour markers or DNA

mutations

CANCER STAGING

* After diagnosis have been made, staging

perform to determine the extend of the disease

progression and evaluate the best treatments

* T: 1-4 For size of tumour(Larger number indicate

larger tumours and spread

* N 0-2 For presence of tumour in lymph nodes

(Larger number indicate spread)

•Ml given to metastases (0 indicate not

spreading)

Cancer Detection and Diagnosis

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Early Cancer May Not Have Any Symptoms

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Cervical Cancer Screening

NormalPap smear

AbnormalPap smear

Breast C

ancer Screening

Colon Cancer Screening

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Biopsy

or blood sample Genomic profile

Microscopic Appearance of Cancer Cells

Normal Cancer

Large number of irregularlys^aPec* div'd'ng cells

a Large, variably shaped nuclei

a Small cytoplasmic volumerelative to nuclei

Variation in cell size and shape

Loss of normal specializedcell features

^ Disorganized arrangement

Poorly defined tumor boundary

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Tumor Grading

100%

General Relationship BetweenTumor Grade and Prognosis

PatientSurvival

Rate

Low grade

High grade

Years

Tumor Staging

100%

50%

Five-Year Survival Rates forPatients with Melanoma (by stage)

I II III

Stage at Time of Initial Diagnosis

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What Causes Cancer?

Some viruses or bacteria

Some chemicals Radiation

Artwork by Jeanne Kelly. © 2004.

ROLES OF DNA DAMAGE ANDMUTATION

• Radiation

• Chemicals

• Environmental toxins

Others

RADIATION

• Examples such as: X rays, CT scan, UV,

radon (radioactive gas)

* Production of Free radicals - atoms with

unpaired electrons

* Antitoxin such as some vitamins

CHEMICALS AND ENVIRONMENTAL

TOXINS

• Chemicals such as mustard gas,hair dyes, chemotherapy drugs

• Environmental toxins such as tarfrom cigarette, coal etc

OTHERS

• Virus such as oncoviruses examples Epstein-Barr virus(EBV), Human papillomavirus (HPV), mouse mammarytumour virus (MMTV)

• Specific virus to cancer types

• Hepatitis B,C (Liver Cancer)

• HPV (Cervical Cancer)

• EBV (Lymphatic Cancer)• Kaposi sarcoma herpes virus (Kaposi sarcoma skin

cancer)

• Human T lymphotrophic Virus 1 (T cell leukemia)

Viruses

Virus insertsand changesgenes forcell growth

Cancer-linked virus

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Examples of Human Cancer Viruses

Some Viruses Associated with Human Cancers

Virus Type of Cancer

Epstein-Barr virus Burkitt’s lymphoma

Human papillomavirus Cervical cancer

Hepatitis B virus Liver cancer

Human T-celllymphotrophic virus

Adult T-cell leukemia

Kaposi’s sarcoma-associated herpesvirus

Kaposi’s sarcoma

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AIDS and Kaposi’s Sarcoma

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Bacteria and Stomach Cancer

Artwork bv can c Koiiy. 2004 Patient’s tissue H. pylorisample

Heredity and Cancer

■ Inherited factor(s)■ Other factor(s)

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Heredity Can Affect Many Types of Cancer

Inherited Conditions That Increase Risk for Cancer

Name of Condition Type of Cancer

Hereditary retinoblastoma Retinoblastoma

Xeroderma pigmentosum Skin

Wilms’ tumor KidneyLi-Fraumeni syndrome Sarcomas, brain, breast,

leukemia

Familial adenomatouspolyposis

Colon, rectum

Paget’s disease of bone Bone

Fanconi’s aplastic anemia Leukemia, liver, skin

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Genetic Testing

Cancer Risk and Aging

Number ofCancer Cases(per 100,000

people)

Cancer Risk and Aging400

300

200

100

0 20 40 60 80

Age of Person (in years)

DNA Mutation

Normal gene

C G A A C T

Single base change

Deletions

Normal cell

Cancer cell

Oncogenes

Mutated/damaged oncogene

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Proto-Oncogenes and Normal Cell Growth

Normal Growth-Control Pathway

Growth factor

Receptor

Cell nucleus

0 Signaling enzymes

Transcriptionfactors

DNA

ell t

Cell proliferatio

Oncogenes areMutant Forms of Proto-Oncogenes

Inactive growth factor receptor Inactive intracellularsignaling protein

Signaling protein from active oncogene

Cell proliferation driven byinternal oncogene signaling

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Normalgenes

preventcancer

Remove or inactivate tumorsuppressor genes

Damage toboth genesleads tocancer

Normal cell

Tumor Suppressor GenesAct Like a Brake Pedal

Growth factor

Receptor

Cell nucleus

Tumor Suppressor

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p53 Tumor Suppressor ProteinTriggers Cell Suicide

Normal cell Excessive DNA damage Cell suicide(Apoptosis)

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Base pairmismatch

Cancer Tends to Involve Multiple Mutations

Benign tumor cells Malignant cells invadegrow only locally and neighboring tissues, entercannot spread by blood vessels, and metastasize

to different sitesinvasion or metastasis

Time

Mutation Cells Mutations Proto-oncogenes More mutations,inactivates proliferate inactivate mutate to oncogenes more geneticsuppressor DNA repair instability,gene genes metastatic

disease

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Mutations and Cancer

Genes Implicated in CancerThe prime suspects But

Mutations in: Other mutations also occur in:

Oncogenes Cell death genes

■ Tumor suppressor genes Cell signaling genes

■ DNA repair genes Cell cycle checkpoint genes

Cellular senescence genes

■ Cellular differentiation genes

■ Metastasis/invasion genes

Carcinogen-activating genes-deactivating genes A

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Cancer Tends toCorrupt Surrounding Environment

Blood vessel Cytokines!

Growth factors = proliferationInvasive

Matrix

Fibroblasts,adipocytes

Cytokines, proteases = migration & invasion

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TREATMENTS

* Surgery

* Radiation

* Chemotherapy

* Others

SURGERY

• Removal of solid cancerous tumour as

much as possible

* Exception include blood cancer such as

leukaemia

RADIATION

* Use of high energy waves to kill or inhibit cell

division

* External beam or seed radioactive within the

tumour

* Trigger apoptosis due to DNA damage but affects

normal cells

CHEMOTHERAPY

* Use of drugs to treat cancer

* Side effects include hair loss, nausea

* Damage DNA

* Interfere with DNA replication

* Interfere with cell division

CHEMOTHERAPY

* Cisplatin (Platinol) for DNA damage

* Doxorubicin (Adriamycin) for DNA

damage

* 5 fluorouracil (Efudex, Adrucil) inhibit

DNA replication* Paclitaxel (Taxol) inhibit mitosis

* Vinblastine (Velban) inhibit mitosis

OTHERS

• Bone marrow Transplantation

• Targeted Therapies

• Tumour Vaccines

• Gene Therapy

BONE MARROW TRANSPLANTATION

• Leukaemia

• Lymphoma

• Stem cells are often damage after

chemotherapy and radiation

• Taken before patient and put back after

treatment

TARGETED THERAPIES

• Pharmacogenomics

• Specialized treatment based onhuman genetics

• Fewer side effects

TUMOUR VACCINE

• Prevent infection example from oncovirus

* Gardasil for cervical cancer as it target

HPV

GENE THERAPY

* Introduction of DNA to allow protein to be

made to overcome disease• P53

Clinical Trails