ONCOLOGY

What Is Cancer?
 CANCER DIAGNOSIS

The term Cancer has been use to

describe over 100 different diseases
characterized by uncontrolled cell
growth
 WARNINGS SIGNS

Weight loss
Persistent Fever
Fatigue
Sores
Bowel patterns
Pain
Indigestion
Lump
Unusual bleeding
 Different Kinds of Cancer

Leukemias:
Some common
Bloodstream
carcinomas:
Lung Lymphomas:
Lymph nodes
Breast (women)

Colon
Some common
Bladder sarcomas:
Prostate (men) Fat
Bone
Muscle
Artwork by Jeanne Kelly. 2004.
 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 -
 Loss of Normal Growth Control

Normal
cell division

Cell Suicide or Apoptosis

Cell damage-
no repair

Cancer
cell division

Artwork by Jeanne Kelly. 2004.

First Second Third Fourth or
mutation mutation mutation later mutation
Uncontrolled growth
 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

___ Jjaa

Artwork by Jeanne Kelly. 2004.

Time
Why Cancer Is Potentially Dangerous

Brain

Melanoma
cells travel
through
bloodstream

Liver
Melanoma
(initial tumor)

Artwork by Jeanne Kelly. 2004.

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 CELL
DEATH (APOPTOSIS)

Death signals

p53
 UNLIMITED CELL DIVISION

* Telomeres

Telomerases
 SUSTAINED ANGIOGENESIS
(STIMULATION OF BLOOD VESSEL
GROWTH)

VEGF (Vascular Endothelial Growth

Factors)

Nutrient, oxygen
TISSUE INVASION AND METASTASIS

* 90% of cell death due to single cell

mutation

Migration
 COMMON DIAGNOSTIC TESTS

Blood test
Imaging test
Biopsy
Cancer Staging
 BLOOD TESTS

Tumour markers - protein that are

found to be elevated in certain
cancer

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

Artwork by Jeanne Kelly. 2004.

Early Cancer May Not Have Any Symptoms

Artwork by Jeanne Kelly. 2004.

Cervical Cancer Screening

Normal
Pap smear

Abnormal
Pap smear
Breast Cancer Screening
 Colon Cancer Screening

Artwork by Jeanne Kelly. 2004.

 Biopsy
Artwork by Jeanne Kelly. 2004.

or blood sample Genomic profile

Microscopic Appearance of Cancer Cells
Normal Cancer
Large number of irregularly
s^aPec* div'd'ng cells

a Large, variably shaped nuclei

Small cytoplasmic volume

a relative to nuclei

Variation in cell size and shape

Los
s of
nor
mal
spe^ Disorganized arrangement

2004.
cial
ize
d
Poorly defined tumor boundary
cell
feat
ure
s
 Tumor Grading
General Relationship Between
Tumor Grade and Prognosis
100%

Low grade

Patient
Survival
Rate
High grade

Years
 Tumor Staging
Five-Year Survival Rates for
Patients with Melanoma (by stage)
100%

50%

Artwork by Jeanne Kelly. 2004.

I II III
Stage at Time of Initial Diagnosis
 What Causes Cancer?
Some viruses or bacteria

Some chemicals Radiation

Artwork by Jeanne Kelly. 2004.

 ROLES OF DNA DAMAGE AND
MUTATION

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 tar

from cigarette, coal etc
 OTHERS
Virus such as oncoviruses examples Epstein-Barr virus
(EBV), Human papillomavirus (HPV), mouse mammary
tumour 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 inserts

Artwork by Jeanne Kelly. 2004.

and changes
genes for
cell growth
Cancer-linked virus
Examples of Human Cancer Viruses

Some Viruses Associated with Human Cancers

Virus Type of Cancer
Epstein-Barr virus Burkitts lymphoma
Human papillomavirus Cervical cancer
Hepatitis B virus Liver cancer
Adult T-cell leukemia
Human T-cell

Artwork by Jeanne Kelly. 2004.

lymphotrophic virus
Kaposis sarcoma
Kaposis sarcoma-
associated herpesvirus
 AIDS and Kaposis Sarcoma

Artwork by Jeanne Kelly. 2004.

 Bacteria and Stomach Cancer

Ar t wor k bv ca n c Koi i y. 2004 Patients tissue H. pylori

sample
 Heredity and Cancer

Artwork by Jeanne Kelly. 2004.

Inherited factor(s)
Other factor(s)
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 Kidney
Li-Fraumeni syndrome Sarcomas, brain, breast,
leukemia
Familial adenomatous Colon, rectum
polyposis

Artwork by Jeanne Kelly. 2004.

Pagets disease of bone Bone
Fanconis aplastic anemia Leukemia, liver, skin
Genetic Testing
 Cancer Risk and Aging

Cancer Risk and Aging

400

Number of 300
Cancer Cases
(per 100,000
people) 200

100

0 20 40 60 80
Age of Person (in years)
DNA Mutation

CT AACT

Normal gene

CG AACT
Single base change

Deletions
 Oncogenes

Normal cell

Cancer cell

Artwork by Jeanne Kelly. 2004.

Mutated/damaged oncogene
Proto-Oncogenes and Normal Cell Growth
Normal Growth-Control Pathway

Growth factor

Receptor
0 Signaling enzymes
Transcription
factors
DNA
Cell nucleus

ell t
Cell proliferatio
 Oncogenes are
Mutant Forms of Proto-Oncogenes
Inactive growth factor receptor Inactive intracellular
signaling protein

Signaling protein from active oncogene

Artwork by Jeanne Kelly. 2004.

Cell proliferation driven by
internal oncogene signaling
 Normal cell Normal
genes
prevent
cancer

Remove or inactivate tumor

suppressor genes

Damage to
both genes
leads to
cancer
 Tumor Suppressor Genes
Act Like a Brake Pedal
Tumor Suppressor

Growth factor

Receptor

Cell nucleus

Artwork by Jeanne Kelly. 2004.

 p53 Tumor Suppressor Protein
Triggers Cell Suicide

Artwork by Jeanne Kelly. 2004.

Normal cell Excessive DNA damage Cell suicide
(Apoptosis)
Base pair
mismatch
Cancer Tends to Involve Multiple Mutations
Benign tumor cells Malignant cells invade
grow only locally and neighboring tissues, enter
cannot spread by blood vessels, and metastasize
invasion or metastasis to different sites

Artwork by Jeanne Kelly. 2004.

Time

Mutation Cells Mutations Proto-oncogenes More mutations,

inactivates proliferate inactivate mutate to oncogenes more genetic
suppressor DNA repair instability,
gene genes metastatic
disease
 Mutations and Cancer

Genes Implicated in Cancer

The 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

Artwork by Jeanne Kelly. 2004.

Carcinogen
-activating genes
-deactivating genes
 Cancer Tends to
Corrupt Surrounding Environment

Growth factors = proliferation

Invasive

Matrix

Fibroblasts,
adipocytes Blood vessel Cytokines!

Artwork by Jeanne Kelly. 2004.

Cytokines, proteases = migration & invasion
 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 on
human 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