ONCOLOGY - biological hallmarks of cancer Flashcards
EXAM 2 content
what are the hallmarks of cancer due to genomic alterations?
- sustained proliferative signaling
- evading growth suppression
- genomic instability
- replicative immortality
genetic mutations are required for cells to become cancer – hereditary or sporadic
sustained proliferative signaling due to genomic alterations: what is going on? what happens normally?
NORMALLY: proto-oncogenes = genes directing normal cell proliferation
CANCER:
- oncogenes = mutated proto-oncogenes –> uncontrolled cell proliferation
- autocrine stimulation: secretes growth factors
ability to evade growth suppressors due to genomic alterations: what is going on? what happens normally?
NORMALLY: anti-oncogenes = tumor suppressor genes
- humans have 2 copies
- regulates cell cycles
- inhibits proliferation
- stops dividing if cells damage
- prevents mutations
CANCER: inactivates anti-oncogenes –> escapes & irregular cell growth
genomic instability due to genomic alterations: what is going on? what happens normally?
NORMALLY: caretaker genes = protects integrity of genome & DNA repair
CANCER: mutations of caretaker genes –> incr genomic instability –> promotor regions change –> silence or altered gene expression –> chromosome instability –> incr cancer risks
replicative immortality (unlimited cell division) due to genomic alterations: what is going on? what happens normally?
NORMALLY: telomeres prevent unlimited cell division (good thing!) allows cells to die eventually
CANCER: telomerase (enzyme) holds telomeres in PLACE, to stay dead –> ALLOWING unlimited cell division –> replicative immortality
- telomerase activity is restored in 90% of all cancers
what are the hallmarks of cancer due to SECONDARY to genomic change?
- angiogenesis
- reprogramming energy metabolism
angiogenesis due to secondary to genomic change: what is going on? what happens normally?
NORMALLY:
- angiogenic factors + angiogenic inhibitors = control development of new vessels
CANCER:
- maintains secretion of angiogenic factors –> promotes new blood vessels
- suppresses angiogenesis inhibitors
reprogramming of energy metabolism due to secondary to genomic change: what is going on? what happens normally?
NORMALLY: oxidative phosphorylation + glycolysis to make ATP for cells
- OXPHOS = most efficient & aerobic
- glycolysis = less efficient & anaerobic
CANCER: oncogenes drive metabolic reprogramming to increase cancer cell proliferation & survival
- Warburg effect = aerobic glycolysis –> products for rapid cell growth
- Reverse Warburg effect = use OXPHOS + glycolysis
what are the hallmarks of cancer due to tumor resistance to destruction?
- resistance to apoptotic cell death
- tumor promoting inflammation
- avoiding immune destruction
resisting apoptotic cell death due to tumor resistance to destruction: what is going on? what happens normally?
NORMALLY: apoptosis is programmed, cells self destruct for tissue remodeling or protection
CANCER: apoptotic pathways are dysregulated
tumor promoting inflammation due to tumor resistance to destruction: what is going on?
chronic inflammation is important for cell development
- organs more susceptible to oncogenic effects of inflam: GI, prostate, thyroid gland
- tumors can alter inflammation for better growth
- infection (H pylori, HIV, hep B & C)
- recruiting local & distinct immune cells for inflammation
evading immune destruction due to tumor resistance to destruction: what is going on? what happens normally?
NORMALLY: immune system protects against cancer thru T cells & NK cells
CANCER: lack of tumor recognition by T cells
- tumor infiltrating lymphocytes, promotes cancer development: remodeling tissue, promoting metastasis, & forming blood vessels
biggest hallmark – CULMINATION of others, whats happening?
invasion = prerequisite for metastasis
- local invasion by direct tumor extension –> invasion of surrounding tissues
metastasis = primary site to distant site, must be able to invade local blood & lymphatic vessels, inflammation –>
- increased migratory capacity
- resistance to apoptosis
- de-differentiation of cells
