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3.1.3.A Understanding Cancer
What is Cancer
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What Is Cancer?
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Different Kinds of Cancer
Lung
Breast (women)
Colon
BladderProstate (men)
Some common sarcomas:Fat
Bone
Muscle
Lymphomas:Lymph nodes
Leukemias:Bloodstream
Some common carcinomas:
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Cancer is Complex
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Naming Cancers
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
Cancer Prefixes Point to Location
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Loss of Normal Growth Control
Cancer cell division
Fourth orlater mutation
Third mutation
Second mutation
First mutation
Uncontrolled growth
Cell Suicide or Apoptosis
Cell damage—no repair
Normal cell division
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Example of Normal Growth
Cell migration
Dermis
Dividing cells in basal layer
Dead cells shed from
outer surface
Epidermis
Balance between cell death and cell production
Cell Division
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The Beginning of Cancerous Growth
Underlying tissue
basal cells now divide faster than is needed to replenish the cells being shed from the surface of the skin.
Both daughter cells retain capacity to divide.
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Tumors (Neoplasms)
Underlying tissue
Neoplasm (new formation/creation)
Increased rate of cell divisionDecreased (or no) apoptosis to compensate
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Invasion and Metastasis
3Cancer cells reinvade and grow at new location
1Cancer cells invade surrounding tissues and blood vessels
2Cancer cells are transported by the circulatory system to distant sites
Cancers spread using 2 mechanisms: • invasion• metastasis
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Invasion - direct migration and penetration by cancer cells into neighboring tissues.
Metastasis - ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through the bloodstream, and then invade normal tissues elsewhere in the body.
Invasion and Metastasis
VIDEO
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Malignant versus Benign Tumors
Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
Time
Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis
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By definition the term “cancer” applies only to malignant tumors
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Why Cancer Is Potentially Dangerous
Melanoma cells travel through bloodstream
Melanoma(initial tumor)
Brain
Liver
Cancer cells in the liver would be called metastatic melanoma, not liver cancer.
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Genes and Cancer
Chromosomes are DNA molecules
Heredity
RadiationChemicals
Viruses
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DNA Structure
DNA molecule
Chemicalbases
GC
TA
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DNA Mutation
Additions
Deletions
Normal gene
Single base change
DNA
CT
A G C G A A C TAC
A G G C G C T AAC A C T
A G C T A A C TAC
A G A A C TAC
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Oncogenes
Mutated/damaged oncogene
Oncogenes accelerate cell growth and division
Cancer cell
Normal cell Normal genes regulate cell growth
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An oncogene is a gene that has the potential to cause cancer.
Categories:Growth factors - Induces cell proliferationReceptor tyrosine kinases – Cell signalingCytoplasmic tyrosine kinases – Cell signalingCytoplasmic Serine/threonine kinases – Cell signalingRegulatory GTPases – Cell signalingTranscription factors – Regulates gene transcription
In tumor cells oncogenes are often mutated or expressed at high levels.
Oncogenes
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Most normal cells undergo apoptosis
Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead
Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer
1970 – First oncogene identified (dozens identified since)
Many cancer drugs target proteins encoded by oncogenes.
Oncogenes
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Proto-Oncogenes and Normal Cell Growth
Receptor
Normal Growth-Control Pathway
DNA
Cell proliferation
Cell nucleus
Transcriptionfactors
Signaling enzymes
Growth factor
A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression
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Oncogenes areMutant Forms of Proto-Oncogenes
Cell proliferation driven by internal oncogene signaling
Transcription
Activated gene regulatory protein
Inactive intracellular signaling protein
Signaling protein from active oncogene
Inactive growth factor receptor
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Tumor Suppressor Genes
Normal genes prevent cancer
Remove or inactivate tumor suppressor genes
Mutated/inactivated tumor suppressor genes
Damage to both genes leads to cancer
Cancer cell
Normal cell
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Individuals who inherit an increased risk of developing cancer often are born with one defective copy of a tumor suppressor gene.
Because genes come in pairs (one inherited from each parent), an inherited defect in one copy will not lead to cancer because the other normal copy is still functional.
But if the second copy undergoes mutation, the person then may develop cancer because there no longer is any functional copy of the gene.
Tumor Suppressor Genes
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Tumor Suppressor GenesAct Like a Brake Pedal
Tumor Suppressor Gene Proteins
DNACell nucleus
Signalingenzymes
Growth factor
Receptor
Transcriptionfactors
Cell proliferation
Restrains cell growth and
division
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p53 Tumor Suppressor ProteinTriggers Cell Suicide
Normal cell Cell suicide(Apoptosis)
p53 protein
Excessive DNA damage(repair not possible)
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DNA Repair Genes
Cancer
No cancer
No DNA repair
Normal DNA repair
Base pair mismatch
T CATC
A GTCG
T CAGC
A GTCG
A GTG A GTAG
T CATCT CATC
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Xeroderma pigmentosum • Inherited defect in a DNA repair gene. • Patients cannot effectively repair the
DNA damage that normally occurs when skin cells are exposed to sunlight
• Exhibit an abnormally high incidence of skin cancer
DNA Repair Genes
Certain forms of hereditary colon cancer also involve defects in DNA repair.
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Cancer Tends to Involve Multiple Mutations
Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
More mutations, more genetic instability, metastatic disease
Proto-oncogenes mutate to oncogenes
Mutations inactivate DNA repair genes
Cells proliferate
Mutation inactivates suppressor gene
Benign tumor cells grow only locally and cannot spread by invasion or metastasis
Time
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Mutations and Cancer
Genes Implicated in Cancer
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Cancer Tends toCorrupt Surrounding Environment
Growth factors = proliferation
Blood vessel
Proteases
Cytokines
Matrix
Fibroblasts, adipocytes
Invasive
Cytokines, proteases = migration & invasion