cancer

• Cancer


  A huge array of diseases with various causes and factors, though all are disorders of cell cycle control
• Infectious causes of cancer have been long suspected, though infection with one of these microbes does not necessarily mean a person will get cancer
• Carcinogenesis


  Formation of a cancer; normal cells are transformed into cancer cells due to action of any one, or a combination, of chemical, physical, biological, and/or genetic factors
• Carcinogenesis occurs in a minority of infected individuals
• Average human cells

  • Can copy itself ~50 times before it dies
  • Uncontrolled cell division can lead to masses of cells (tumours)
• Cell division is under strict genetic control; cells are prevented from unlimited division
• Carcinogenesis


  1. Initiation - an irreversible genetic alteration occurs in cell

  2. Promotion - involves changes in expression of the genome (not in the structure of DNA); mediated through promoter-receptor interactions; is reversible at this stage

  3. Progression - irreversible; characterized by malignant growth
• Genes involved in cancer

  • Proto-oncogenes
  • Oncogenes
  • Tumor suppressor genes
• Proto-oncogenes


  Genes in normal cells that encode various types of proteins that stimulate normal cell growth and division
• Oncogenes


  What proto-oncogenes are called once activated
• Oncogenes

  • They integrate their DNA into the host cell's genome
  • May inhibit normal cell death (apoptosis)
  • May supress the host immune system
  • May lead to uncontrolled cell growth/division
• Environmental factors that contribute to the activation of oncogenes

  • Ultraviolet light
  • Radiation
  • Carcinogens
  • Viruses
• Tumour Suppressor Genes


  Normal genes that slow down cell division, repair DNA mistakes, or trigger programmed cell death (apoptosis)
• If tumour suppressor genes don't work, uncontrolled cell growth can occur, leading to cancer
• Oncogenes vs Tumour Suppressor Genes

  • Oncogenes result from the activation (turning on) of proto-oncogenes
  • Tumor suppressor genes cause cancer when they are inactivated (turned off)
• Transformation

  • Changes in host cell as a result of mutations or infection with an oncogenic virus
  • Changes relate to cell cycle control
  • May be due to mutation, chromosomal structural changes, or introduction of viral genes
• How viral infections cause certain cancers is not yet fully understood
• Products of proto-oncogenes

  Accelerate cell cycle progression
• Loss of cell cycle control

  Results in uncontrolled cell division
• Tumour suppressor genes

  Encode proteins eg p53, to stop the cell cycle to allow for DNA repair, or if this is not possible, they can induce apoptosis (programmed cell death)
• Mutation or inhibition of tumour suppressors can cause loss of cell cycle control and lead to uncontrolled proliferation of cells and development of tumours
• p53 protein


  • A DNA binding protein; allows transcription of genes in the various response pathways for such things as DNA repair, differentiation, cell cycle arrest, and apoptosis in response to stress conditions
  • An important tumour suppressor
  • "the guardian of the genome"
• Majority of human cancers involve a mutant/defective p53
• Some viruses have genes that encode p53 inhibitors
• Cancer cells


  • Lack contact inhibition
  • Divide indefinitely
  • Develop ways to escape the mechanisms that dictate how many times a cell can divide
• Immortal cells


  • Most cells have limits on the number of times they can undergo division (~50) due to telomere shortening
  • Cancer cells are not subject to these limits as they maintain their telomeres using the human telomerase enzyme
• Human telomerase enzyme


  • A type of reverse transcriptase able to add telomere units to the end of the chromosomes
  • Consists mostly of proteins but also contains an RNA molecule the template for building the telomere subunits
• Human telomerase enzyme is found in all cells, but it is inactive (except in germ cells, stem cells, and most cancer cells)
• Neoplasia


  Uncontrolled cell division in multicellular animal
• Tumour


  Mass of neoplastic cells; two types - benign tumors (remain in one place, not harmful) and malignant tumors (aka cancers, harmful, spread to other tissues)
• Metastasis

  In some types of cancer, malignant cells are able to migrate/spread (via the blood or lymph) to a secondary site, invade those tissues and form another tumour
• Cancers rob normal cells of nutrients and space, cause pain, affect normal function of cells/tissues
• Cancer doesn't usually arise form a single event, requires multiple hits aka mutations over a period of time
• Some individuals are more at risk as they already have certain mutations that predispose them to these changes
• Colon cancer development


  Over time, changes in tumour suppressor genes and/or activation of oncogenes, might lead to a malignant carcinoma to develop from a benign polyp
• Hallmarks of Cancer


  • Self-sufficiency in growth signals
  • Insensitivity to growth-inhibitory signals
  • Evasion of programmed cell death (apoptosis)
  • Limitless replication potential
  • Sustained tumour angiogenesis
  • Tissue invasion and metastasis
• More at risk


  Already have certain mutations that predispose them to these changes
• Loss of tumour suppressor gene, oncogene activation, DNA changes

  1. Small adenoma, benign

  2. Carcinoma-malignant tumour with metastasis
• Hallmarks of Cancer

  • Self-sufficiency in growth signals
  • Insensitivity to growth-inhibitory signals
  • Evasion of programmed cell death (apoptosis)
  • Limitless replication potential
  • Sustained tumour angiogenesis
  • Tissue invasion and metastasis
• Several major infectious agents have been identified as human carcinogens by the International Agency for Research on Cancer