Neoplasia Lec 3 Flashcards
what are the 6 hallmarks of cancer
- evading apoptosis
- sustained angiogenesis
- self-sufficiency in growth signals
- insensitivity to anti-growth signals
- tissue invasion and metastasis
- limitless replicative potential
what does G0/G1 in the cell cycle do
cell is quiescent or accumulating building blocks required for division
what does S in the cell cycle do
cell replicates DNA
what does G2 in the cell cycle do
cell assembling machinery for chromosomal segregation and cytokinesis
what is M in the cell cycle
mitosis
what is the cell cycle and what is it driven by
- Determines when cell moves from one phase to next
- Driven by cyclins paired with (CDKs)
- R point (restriction) is critical time point when cells decide to enter or not into cycle
what do checkpoints mean in the cell cycle
Block the passage into next cycle when cells not ready
what does hallmark 1 (self-sufficiency in growth signals) do
- Activation of kinase signal transduction that respond to mitogenic signals (GFs)
GF receptors are RTKs - Activation of RTK
–> Gain of function
—— EGFR in lung cancer
–> Amplification
—— HER2 in breast cancer
what does Hallmark 2 (resistance to growth inhibitory signals) do
- May arise through loff of expression of growth inhibitory proteins (tumor suppressors)
–> TGF-b, p53
–> p16(INK4a)
–> E2F (transcription factor in G1/S)
what does Hallmark 3 (evading apoptosis) do
- Disruption of apoptotic pathways preventing cell death upon DNA damage or cell cycle checkpoint activation
- Tumor suppressors
–> P53 - transcription factor
–> P21 - CDK inhibitor
–> BAX - pro-apoptotic regulator
what does Hallmark 4 (limitless replicative potential) do
- Normal cells can divide only 40-60x (Hayflick limit)
- Telomere shortening leads to chromosomal abnormalities and cell death
–> Loss of genes near end of chromosome - Tumor cells overexpress telomerase, leading to immortalization
what does Hallmark 5 (sustained angiogenesis) do
- Tumor cells can trigger angiogenesis (neovascularization)
- Solid tumors can’t grow beyond 1-2 mm without blood supply
–> Deficient in oxygen/nutrient
–> Unable to get rid of metabolic waste (lactic acid/CO2) - Tumor cells produce VEGF to promote angiogenesis
– HIFa
—> Transcription factor for hypoxia genes (VEGF)
– VHL - von hippel lindau
—> Tumor suppressor E3 ligase for HIFa
what does Hallmark 6 (tissue invasion and metastasis) do
- Adhesion and invasion of basement membrane
- Passage through extracellular matrix
- Invasion of vascular basement membranes and vascular ingress (intravasation)
- Travel via the vasculature
- Adhesion to basement membrane at destination
- Invasion of vascular basement membrane and vascular exit (extravasation)
- Metastatic deposit
- Angiogenesis and growth
what are the three steps in multistep carcinogenesis
- initiation
- promotion
- progression
what is the initiation step
- Exposure of cells to appropriate doses of carcinogenic agent
- Irreversible change in genome
- Amount of total exposure matters
what is the progression step
- Acquisition of malignant characteristics
–> Invasiveness, metastatic competence
what is the promotion step
- Unregulated and accelerated growth of mutated cells
- Triggered by growth factors and chemicals
- May occur after long latency periods
what are the manifestations of cancers
- wasting syndrome
- fatigue and sleep disorder
- anemia
- pain
describe wasting syndrome
- Cancer anorexia-cachexia syndrome)
- Reduced food intake (anorexia) and wasting of body fat and muscle tissue (cachexia)
- Oral or parenteral nutritional supplement does nor reverse cachexia
- Significant cause of morbidity and mortality
describe fatigue and sleep disorder
- Tiredness, weakness, and lack of energy not relieved by sleep or rest
- Poor sleep quality, insufficient sleep, nightmare awakening, and restless sleep
describe anemia
- Blood loss, hemolysis, impaired red blood cell production
- Drugs used in treatment may also decrease red blood cell production
describe pain
- Common in late-stage cancers
- Most dreaded aspects of cancer
- Pain management is necessary even for patients with incurable cancers
what are the methods for targeting cancer therapy
- FISH
- IHC
- DNA sequencing
what are the targeting cancer therapies
- BCR-ABL translocation
- Estrogen receptor (ER)
- HER2 Overexpression
- EFGR mutations
- Ras mutations
