Molecular Basis of Neoplasm

General
1. Nonlethal genetic damage
2. clonal expansion from precursor cell
3. 4 types of regulatory genes
  1. proto-oncogenes
  2. tumor suppressor genes
  3. apoptosis genes
  4. DNA repair
4. accumulation of complementary mutation
  1. driver mutations allow for other mutations to accumulate
  2. passenger mutations
5. evolve and progress under Darwinian selevtion
  1. changes tumor behavior and history of the cancer
6. epigenetic aberrations cause problems too
Cellular and Molecular Hallmarks of Cancer
1. 8 fundamentals of changes
  1. self-sufficiency in growth signals
  2. insensitivity to growth-inhibitory signals
  3. altered cellular metabolism
  4. evasion of apoptosis
  5. limitless replicative potential (Immortality)
  6. sustained angiogenesis
  7. ability to invade and metastasize
  8. ability to evade host immune response
2. accelerated by genomic instability and cancer-promoting inflammation
Self-Sufficiency in Growth Signals: Oncogenes
1. mutations in proto-oncogenes
  1. oncogenes
    1. promote cell growth in the absence of growth-promoting signalling
  2. Mutations in...
    1. G protein coupled
    2. JAK/STAT
    3. WNT
    4. Notch
    5. TGFb/SMAD
    6. Hedgehog
    7. NF-kB
Proto-oncogenes, Oncogenes, Oncoproteins
1. drive proliferation
2. Mutations of...
  1. Growth Factors
    1. can synthesize GF on their own
  2. Growth Factor Receptors
    1. become constitutively active
  3. Down stream components of TK signaling pathway
  4. RAS mutations
    1. signal transmitting protein
    2. reduced GTPase activity
  5. BRAF and PI3K
    1. BRAF
      1. serine/threonine kinase
      2. stimulate downstream kinases
    2. PI3K
      1. activates AKT
      2. PTEN mutation removes regulation
  6. Nonreceptor Tyrosine Kinases
    1. ex: BCR-Abl
    2. same function as receptor TK
  7. Transcription Factors
    1. disregulation of mitotic pathways
  8. MYC oncogene
    1. activates with other cell growth genes
    2. sometimes upregulates telomerase
    3. can be used to reprogram somatic cells backwards
  9. Cyclins and CDK
    1. stop having cell cycle checkpoints
      1. promotes progression
Insensitivity to Growth Inhibition: Tumor Suppressor Genes
1. normally stop growth
2. two-hit hypothesis
  1. two mutations are required to cause symptoms
  2. sporadic or familial
3. RB: governs proliferation
  1. negative regulation on G1/S transition
  2. hyper/hypophosphorylated
4. TP53
  1. regulates cell cycle progression, DNA repair, cellular senescence and apoptosis
  2. Enter text here
Growth-Promoting Metabolic Alterations: The Warburg Effect
Evasion of Programmed Cell Death (Apoptosis)
Limitless Replicative Potential: The Stem Cell-Like Properties of Cancer Cells
Angiogenesis
Invasion and Metastases
Evasion of Host Defense
Genomic Instability
Cancer-Enabling Inflammation
Dysregulation of Cancer-Associated Genes
Molecular Basis of Multistep Carcinogenesis

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Molecular Basis of Neoplasm

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	Creado por Jeff Amos hace casi 10 años