8489 Materi Kuliah FK Umi

Cancer
Dr. Sumihar Pasaribu, M.Biomed
Departemen Biokimia FK-UMI Medan

What Is Cancer?
 Cancer is a large group

of diseases (over 200)
characterized by
uncontrolled growth and
spread of abnormal
cells.*
*American Cancer Society, Cancer Facts and Figures 2005

Normal Cells Vs. Cancer Cells
 Cancer cells:
 Lose control over growth
and multiplication
 Do not self-destruct when

they become worn out or
damaged
 Crowd out healthy cells

Growth of Cancer Cells
 Cancer cells reproduce
every 2-6 weeks.
2-6 weeks
 Size of cancer cells:
 One million cancer
2-6 weeks cells = head of a pin
 One billion cancer

cells = a small grape
 230 = 1,073,741,824
= 1 billion cells
2-6 weeks
Signs and Symptoms of Cancer
 Change in bowel habits or bladder functions
 Sores that do not heal
 Unusual bleeding or discharge
 Lumps or thickening of breast or other parts of
the body
 Indigestion or difficulty swallowing
 Recent change in wart or mole
 Persistent coughing or hoarseness
Types of Cancers
 Carcinomas (cells
that cover internal and
external body surfaces) Leukemia
(Blood Cells)
Lung
Lymphomas
Breast (Lymph nodes &tissues)
Colon
Bladder
Prostate Sarcomas
(Men) Cells in supportive
tissues – bones &
muscles
What Causes Cancer?
Family History
Lifestyle
Environment
What Causes Cancer?
 External Factors – chemicals, radiation,
viruses, and lifestyle
 Internal Factors – hormones, immune
conditions, and inherited mutations
 Theories
 Cellular change/mutation theories
 Carcinogens
 Oncogenes/ protooncogenes
Factors Believed to Contribute to Global
Causes of Cancer
Figure 16.2
Cancer pathogenesis
 Oncogenes
 myc, ras, src, abl, bcl2
 Tumor suppressor genes
 p53, Rb, APC, MEN1, NF1
 MicroRNA
 Transcriptome control
The path to cancer
 Clonal proliferation
 Starts from a single cell
 Expansion in steps
 Pre-malignant states
 Polyp, MDS, MGUS
 Serial accumulation of mutations
 Clonal evolution
 Resistance
“Hallmarks of cancer”
 Self-sufficiency in growth signals

 Insensitivity to anti-growth signals
 Evading apoptosis
 Limitless reproductive potential
 Sustained angiogenesis
 Tissue invasion and metastases
 Genomic instability
Hanahan & Weinberg, 2000
Tissue and tumor architecture
Dingli & Pacheco, 2008

Cancer stem cells
 Present in most (all) tumors

 Small fraction of population
 No universal marker
 Often resistant to therapy
 May be important target of therapy
 Cancer initiating cells in mice
Genomic instability
 Is it necessary?
 Normal vs abnormal mutation rate
 2 current views
 Chromosomal instability
 Gross translocations, loss and gain of
chromosome parts
 Mutator phenotype
 Repair genes
 Xeroderma pigmentosum
 MMR etc
Cytogenetic abnormalities
 Translocations
 Balanced
 Reciprocal
 Aneuploidy
 Pseudodiploid
 Hyperdiploid
 Complex
 Random loss or gain

Limitless reproductive potential
 Hayflick hypothesis
 Limited number of doublings
 Telomere maintenance
 Telomerase
 Not all tumor cells have this potential

 Tumor stem cells
Self-sufficiency in growth
signals
• Autocrine loops
• Over-expression of
receptor
• Receptor is always
‘on’
• Downstream
signals
Insensitivity to antigrowth signals
Evading apoptosis
 External triggers
 Intracellular triggers
 Death receptors
 Caspases
 Sensors (8, 9)
 Executioners (3)
Sustained angiogenesis
 VEGF
 FGF1/2
 Thrombospondin
 Thalidomide
 Avastin
Tissue invasion and metastases
Tumor burden - Staging
 Tumor
 Size, capsule invasion
 Nodes
 Involved, how many?
 Metastases
 Present/absent
 “Unknown primary”
Imaging
 CT scan
 PET/CT
 SPECT/CT
 MRI
 Staging
 Response
Prognostic scoring systems
 Host vs Disease
 Disease burden
 Disease biology
 Co-morbid conditions
 Performance status
Good News!
Other Ways to Reduce

the Risks of Developing
Cancer…
How Far Have We Come ?
Five year survival
rate:
 1913 - 10%
 2003 - 66%
 Advances in cancer
research continue
The Fight Will Continue
Because…in 2007
 Cancer is the second
leading cause of death in
Utah and the nation
 7660* Utahns diagnosed
 2690* Utahns will die
 7 Utahns die of cancer

every day
*American Cancer Society, Cancer Facts and Figures 2007

Avoid Smoking or Chewing
Tobacco
 Cigarette smoking is the

leading cause of preventable
death in the US
 Second hand smoke affects
everyone
Fruits and Vegetables
Decrease Cancer Risks
 Cancer rates could
decline by up to
20% if everyone
consumed 5 fruits and
vegetables a day!*
 Cancer fighting
substances:
 Antioxidants
 Dietary fiber
 Carotenoids
*American Institute for Cancer Research, 1998.
 Flavenoids
Limit Alcohol to No More Than
 Men – 2 drinks per

day
 Women - 1 drink per

day
Reduce Your Skin Exposure to
the Sun
 Limit time outside,
between 10 a.m. & 4 p.m.
 Wear protective clothing.
Use wide-brimmed hats
and sunglasses.
 Prevent sunburns,
especially for children
under 18. Use
waterproof sunscreen of
SPF 15 or higher.
Reapply as directed.
 Avoid tanning beds.
Be Active…Often
 Exercise for 30 minutes or
more at least 4 days a
week.
186,550
The number of lives that could be
saved each year if we ate a healthy
diet and exercised regularly
186,550
The number of lives that could be
saved each year with no tobacco
American Cancer Society

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Cancer

Dr. Sumihar Pasaribu, M.Biomed

Departemen Biokimia FK-UMI Medan

 Cancer is a large group

*American Cancer Society, Cancer Facts and Figures 2005

 Do not self-destruct when

 Crowd out healthy cells

 One billion cancer

 Self-sufficiency in growth signals

Dingli & Pacheco, 2008

 Present in most (all) tumors

 Random loss or gain

 Not all tumor cells have this potential

Other Ways to Reduce

 7660* Utahns diagnosed

 2690* Utahns will die

 7 Utahns die of cancer

*American Cancer Society, Cancer Facts and Figures 2007

 Cigarette smoking is the

 Men – 2 drinks per

 Women - 1 drink per

American Cancer Society

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