Cancer pathology

• Who is the lecturer for the Introduction to Cancer course?

  Professor Phil Dash
• What are the main topics covered in the Introduction to Cancer lecture overview?

  • What is cancer?
  • Hallmarks of cancer
  • Causes of cancer
  • Types and stages of cancer
  • Treatments
• What is the common feature of cancer?

  An uncontrolled increase in cell number leading to invasion of surrounding tissues and metastasis
• How does cancer affect cell control?

  Cancer is a disease where we lose control over our own cells
• What are the hallmarks of cancer?

  1. Self-sufficiency in growth signals

  2. Limitless replicative potential

  3. Insensitivity to antigrowth signals

  4. Resistance to apoptosis

  5. Angiogenesis

  6. Invasion and metastasis

  7. Immune avoidance
• What is the role of growth factors in cell proliferation?

  Growth factors are signals that cells receive to proliferate
• What happens to cells in the absence of growth signals?

  Cells are not able to proliferate
• What initiates the process of cell proliferation in the presence of growth signals?

  The receptor for the growth factor is switched on and becomes active
• What is the outcome of the sequence of switches initiated by growth signals?

  Changes in gene expression leading to cell proliferation
• What occurs when the growth factor signal is removed?

  All the proteins are switched off and cell proliferation stops
• What is an oncogene?


  An oncogene is a gene that, when mutated or overexpressed, can cause cancer
• What is the effect of mutations in proto-oncogenes?

  They lead to a gain of function
• What is the most common oncogene found in cancer?

  Ras
• What percentage of all tumors have a mutant version of Ras that is permanently switched on?

  20-30%
• What are some examples of oncogenes?

  • Bcr-Abl
  • myc
  • Src
  • PI3 kinase
• How do oncogenes affect cell proliferation?

  They lead to increased activity and cell proliferation in the absence of specific growth signals
• What is the role of telomerase in tumor cells?

  Telomerase rebuilds telomeres, allowing tumor cells to be effectively immortal
• How many cell divisions are typically limited by telomere shortening?

  40-60 cell divisions
• What is the function of tumor suppressor genes?

  Tumor suppressor genes stop tumors from forming
• How many hits are typically required to inactivate a tumor suppressor gene?

  Two hits
• What are examples of tumor suppressor genes?

  p53 and BRCA
• What is the most common mutated gene in cancer?

  p53
• What triggers apoptosis in cells?

  DNA damage and viral infection
• What family of proteins controls the sensitivity of the cell to apoptosis?

  The Bcl-2 family of proteins
• What happens to pro-survival members of the Bcl-2 family in cancer?


  They are commonly over-expressed
• What happens to pro-apoptotic members of the Bcl-2 family in cancer?


  They are commonly mutated and non-functional
• What is angiogenesis?

  Angiogenesis is the formation of new blood vessels
• What is the maximum size of a tumor mass without a blood supply?

  Approximately 10$^6$ cells (2 mm diameter)
• What percentage of cancer deaths are due to metastasis?

  90%
• What distinguishes malignant cells from benign cells?

  The acquisition of invasive properties
• What is the process by which malignant cancer cells move away from the main tumor?

  Cells "crawl" through the extracellular matrix until they reach a blood vessel
• What are the most common sites of metastasis?

  Lung, liver, brain, and bone
• What is the new hallmark of cancer related to immune response?

  Immune avoidance
• How do tumors avoid the immune response?

  By acquiring mutations that change the structure of proteins to make them look non-self
• How often is DNA in a typical cell damaged?

  Around 10,000 times per day
• What happens to most DNA damage in cells?

  Most of this DNA damage is repaired
• What can lead to mutations in key genes such as proto-oncogenes or tumor suppressor genes?

  DNA damage that is occasionally missed during repair
• What are the types of DNA mutations?

  • Point mutations
  • Small insertions/deletions
  • Alterations in transcription/splicing
  • Amplifications/deletions of chromosomal regions
  • Chromosomal translocations
  • Gains and losses of whole chromosomes
  • Changes in DNA modification (e.g., DNA methylation)
• What are some causes of DNA mutations?

  UV radiation, viruses, chemicals, free radicals, and copying/repair errors
• What can accumulated mutations lead to in cancer?

  Genome instability and an increased likelihood of further mutations