{"id":4718,"date":"2017-04-06T15:04:27","date_gmt":"2017-04-06T07:04:27","guid":{"rendered":"http:\/\/https:\/\/medicine.nus.edu.sg\/pathweb\/?page_id=4718"},"modified":"2023-04-03T11:52:39","modified_gmt":"2023-04-03T03:52:39","slug":"ii-how","status":"publish","type":"page","link":"https:\/\/medicine.nus.edu.sg\/pathweb\/pathology-demystified\/neoplasia\/ii-how\/","title":{"rendered":"III. How: Pathogenesis"},"content":{"rendered":"\n\n\t

Cancer cells are genetically-mutated<\/strong> cells that have gained the ability to form malignant tumours (undergone malignant transformation<\/strong>) – i.e. they can break away from normal cellular controls and regulations.<\/p>\n\t\t\t\t\tCharacteristics of Cancer Cells (Click to expand)<\/a>\n\t\t\t\t\t\t\t\t\t\t\tExpand<\/i><\/a>\n\t\t\t\t\t

Cancer cells are:<\/strong><\/p>\n

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  1. Self-sufficient in supply of growth factors<\/li>\n
  2. Insensitive to inhibitory signals against cell growth and proliferation<\/li>\n
  3. Resistant to apoptosis (cell death)<\/li>\n
  4. Immortal<\/li>\n
  5. Able to stimulate formation of new blood vessels for blood supply (angiogenesis)<\/li>\n
  6. Able to invade surrounding tissues and metastasize to distant organs<\/li>\n<\/ol>\n\t

    In order to transform to a cancer cell, the cell must overcome these major protective mechanism<\/strong>s:<\/p>\n

    (1) Cell cycle regulatory checkpoints<\/p>\n

    (2) Tumour suppressing mechanisms<\/p>\n

    (3) Apoptosis (cell death)\u00a0<\/p>\n

    (4) DNA repair mechanisms<\/p>\n

    Malignant transformation\u00a0requires multi-step genetic aberrations <\/strong>(eg. point mutations, gene amplifications, deletions, translocations to chromosomal rearrangements.) In other words, many genes must be affected before it occurs.<\/p>\n

    Some of the key genetic aberrations involve two main groups of genes:<\/strong><\/p>\n\t\t\t\t\tProto-oncogenes (Click to expand)<\/a>\n\t\t\t\t\t\t\t\t\t\t\tExpand<\/i><\/a>\n\t\t\t\t\t

    \"\"<\/p>\n\t\t\t\t\tTumour suppressor genes (Click to expand)<\/a>\n\t\t\t\t\t\t\t\t\t\t\tExpand<\/i><\/a>\n\t\t\t\t\t

    \"tsg2\"<\/p>\n\t

    Many are involved in key events in the life of a cell: Cell cycle regulation, DNA repair and apoptosis. \u00a0<\/em><\/strong>One such gene is\u00a0p53<\/strong>, located on chromosome 17, which is a key tumour suppressor gene which encodes TP53, a protein responsible for cell cycle arrest and promotion of apoptosis as a response to DNA damage. This is the ‘gatekeeper’ of the cell, and plays a big role in guarding against abnormal cell proliferation and neoplastic transformation. \u00a0<\/em><\/p>\n

    But what actually leads to malignant transformation?<\/strong> Please refer to pathology texts or your lecture notes for detailed example<\/em>s.<\/p>\n

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    1. Inherited genetic aberration \u00a0Eg, Inherited cancer syndromes, familial cancers<\/li>\n
    2. Acquired genetic aberrations\n