10 Cancer

• If a firm increases advertising, their demand curve shifts right, increasing the equilibrium price and quantity
• Understanding the multi-step development of cancer

  1. Enables specific interventions for cancer treatment

  2. Involves factors causing cancer, cancer-critical genes, changes leading to cancer, and the multi-step process of cancer development
• Cancer development is a multi-step process
• Cancer


  • Range of diseases characterised by uncontrolled cell division and spread of abnormal cells to surrounding tissues and other parts of the body
  • Described as a genetic disease caused by accumulation of mutations of critical genes leading to uncontrolled cell growth and proliferation
• Cancer is a group of diseases characterised by uncontrolled cell division and metastasis
• Metaphase checkpoint

  Last cell cycle checkpoint to assess if all chromosomes are attached to the mitotic spindle. If Metaphase checkpoint is defective but cell still enters anaphase, it would result in aneuploidy or polyploidy
• G1 checkpoint


  Most important checkpoint at the end of G1 phase to decide if cell should divide or not. If G1 checkpoint is defective but the cell still enters the S phase, the subsequent phases of the cell cycle might not occur properly
• Most cancers originate from a single aberrant cell that proliferates out of control to give rise to primary tumours whose cells eventually metastasise to form secondary tumours
• Benign tumours are non-cancerous and grow locally without spreading to other regions of the body
• There are 2 types of tumours: Benign tumour and Malignant tumour
• The vast majority of cancers are characterised by an accumulation of genetic mutations, which may be inherited if they occur in germ line cells
• G2 checkpoint

  This checkpoint at the end of G2 phase triggers the start of M phase. If G2 checkpoint is defective but cell still enters the M phase when not all chromosomes have been replicated, the chromosome number in daughter cells would be affected
• Dysregulation of cell cycle checkpoints and its link to cancer

  The dysregulation of cell cycle checkpoints can result in uncontrolled cell division where the rate of cell division exceeds cell death, leading to tumour formation
• Malignant tumours invade surrounding tissue and metastasise to other parts of the body
• Mutated proto-oncogenes are known as oncogenes
• The vast majority of cancers are characterised by an accumulation of genetic mutations
• Proto-oncogenes, when mutated, can become oncogenes with new or enhanced activity
• The development of cancer is a multi-step process requiring multiple somatic mutations to produce all the changes characteristic of a full-fledged cancer cell
• Genetic mutations may be acquired in an individual’s lifetime due to errors during cell division or exposure to carcinogens
• These genes either undergo a gain-of-function mutation or a loss-of-function mutation during cancer development
• Gain-of-function mutations cause genes to encode proteins with new or enhanced activity, while loss-of-function mutations cause gene products to be non-functional
• Only one copy of the allele needs to be mutated for gain-of-function mutations, known as dominant mutation, while both copies need to be mutated for loss-of-function mutations, known as recessive mutation
• Genes involved in cancer development


  • Proto-oncogenes
  • Tumour suppressor genes
  • Genes encoding telomerase
  • Genes encoding proteins involved in angiogenesis
  • Genes encoding proteins involved in metastasis
• The table summarises and compares gain-of-function and loss-of-function mutations in cancer development
• Proto-oncogenes are normal cellular genes that code for proteins that stimulate normal cell growth and proliferation
• Gain-of-function mutations affect proto-oncogenes, while loss-of-function mutations affect tumour suppressor genes
• Genetic mutations may be inherited if they occur in germ line cells and can be passed down to the next generation
• How genetic mutations affect normal cells

  1. They can cause a normal cell to continue to divide

  2. They can fail to stop uncontrolled cell growth

  3. They can have mistakes during DNA repair
• Tumour suppressor genes, when mutated, become defective and cannot activate other genes
• Gain-of-function mutations overstimulate the cell cycle, while loss-of-function mutations make cells unable to halt the cell cycle to repair DNA damage
• Mutated tumour suppressor genes contribute to cancer with a loss-of-function mutation, causing the expressed protein to lose its ability to inhibit cell growth and division
• Movement of DNA within the genome

  Chromosomal translocation, Gene transposition, Retroviral integration
• Proto-oncogene products

  • Proteins derived from proto-oncogenes
  • Involved in stimulating normal cell growth and division
  • E.g. Growth factors, growth factor receptors, transcription factors etc.
• Normal ras gene events involve growth factor binding, activation of Ras protein, signal transduction, stimulation of cell cycle, and cell division
• Tumour suppressor genes


  Normal cellular genes that code for proteins that normally inhibit cell growth and division
• Point mutations in proto-oncogene

  Changes the amino acid sequence of the proto-oncogene protein, leading to either more active (hyperactive) or more resistant to degradation (degradation-resistant gene product) than the normal protein
• Gain-of-function mutation


  A mutation that converts proto-oncogene to oncogene, resulting in an increase in the amount of proto-oncogene protein product or the intrinsic activity of the protein product
• Amplification of a proto-oncogene

  Results in an abnormal increase in the number of copies of the proto-oncogene in the cell, leading to excessive production of proto-oncogene protein and promoting excessive cell division
• Mutation mechanisms that lead to oncogene formation

  1. Point mutations in proto-oncogene itself or a control element (e.g. promoter, enhancer or silencer)

  2. Amplification of the proto-oncogene

  3. Movement of DNA within the genome (Chromosomal Translocation, Gene Transposition, Retroviral Integration)
• Oncogenes


  Mutated proto-oncogenes