3.1.3.A Understanding Cancer What is Cancer. What Is Cancer?

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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