What is cancer?

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What is cancer?

• Collection of diseases uncontrolled growth
• Several cellular changes are required to generate
  a tumour
• Lifestyle may be important
• Cell changes continue to develop after cancer
  formed
• Mutations in repressor genes and oncogenes
  important
• Invasion and metastasis

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Lung Cancer
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Melanoma / A skin Cancer
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Breast Cancer
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Leukaemia
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Nobel Prize for Medicine 2006
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Multi-stage carcinogenesis
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Promotion
Initiation
Progression
Expansion
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Lifestyle and Cancer

• Smoking and lung cancer
• Acid reflux and oesophageal cancer
• Sexual activity and cervical cancer
• Dietary fats and colorectal and breast cancer

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Cancer and Genes

• Familial adenomatous polyposis colon cancer
• Familial breast cancer
• Li- Frameini syndrome p-53 mutations

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Factors contributing to uncontrolled growth
Proliferation
Cell Death
Differentiation
Immune ev
Cell
Cell Contact
ECM
Blood Supply
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• Colon cancer is a multi staged event that arises
  from a series of histopathologic and molecular
  changes

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Molecular Events in the Colorectal Adenoma-to
Carcinoma Sequence
p53
Mutation
K-ras
Mutation
DCC loss
DNA Hypomethylation
APC Mutation or loss
Hyperproliferative
Early Adenoma
Late Adenoma
Carcinoma
Normal
Epithelium
Epithelium
From Fearon et al, Cell 1990
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Initiation and Promotion

• Initiation lung cancer, thyroid cancer and
  leukaemis
• Promotion- estrogens in breast cancer
• Tumour Promoters terpenes , bush teas
• Other growth factors

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New and accumulated mutations

• Oncogene mutations
• Tumour suppressor gene deletions
• Loss of Heterozygosity

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Loss of Heterozygosity
Loss of Part of chromosome
Inactivating mutation
X
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Proliferation

• Accumulated mutations increase rate of
  proliferation
• Increasing proliferation increases rate of
  mutation
• Proliferation can be externally driven eg virus
  induced liver cancer

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Cell Death

• Normal cells die through programmed cell death -
  apoptosis
• A complex set of machinery regulates normal cell
  death
• If this is defective defective cells survive

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Differentiation

• Maintained by the interaction of cells with thye
  environment
• Differentiating signals eg retinoic acid
• Break up of differentiation signals results in
  uncontrolled cell death

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Immune attack

• Immune surveillance
• New molecules on surface of epithelial cells
  recognised as foreign
• Lymphocyte attack uses IL-2 and TNF
• Important for certain tumours eg melanoma and EBV
  tumours
• Susceptible to immune suppression eg HIV nutrition

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Melanoma
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Chronic Myeloid Leukaemia
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Stem Cell Chr 22 normal
Bcr-abl Translocation 922
Red Cell lineage
Myeloid Lineage
Chronic Myeloid Leukaemia
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Blood Supply

• Growing tumour needs a blood supply
• The concept of angiogenesis
• VEGF factors produced by tumours

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ANGIOGENESIS
Tumour
VEGF
Endothelium
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INCREASING THE BLOOD SUPPLY
Endothelial cell prolif
Endothelial cell growth
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Metastasis and Invasion

• Tumour uses signaling molecules for migration eg
  CD44, integrins
• Tumour uses chemokines normally found in immune
  system
• Tumour uses matrix metalloproteases

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