cancer and cancer biology Flashcards
what is cancer
a disease in which an abnormal group of cells grow uncontrollably, disregarding the normal rules of cell division
what are the hallmarks of cancer
sustaining proliferative signalling, immortality, evading growth suppressors, invasion and metastasis, angiogenesis, resisting cell death
how do cancers sustain proliferative signalling
eR2B receptors form homodimers and phosphorylated to activate Ras pathway - mutation of Ras = active!
how do cancers evade growth suppressors
- G1 checkpoint mutations in cyclins/CKDs/CDKIs
- Rb protein mutation - usually acts as a break to inhibit entry to S phase - phosphorylation allows cell to continue, deletion/mutation causes cell division because of E2F mediated transcription
- P53 mutations - no apoptosis or DNA fixing
how do cancer cells resist cell death
P53 mutation, accumulation of damaged DNA but no apoptosis
how do cancer cells become immortal
telomerase - enzyme which adds TTAGGG to breaking telomeres - upregulated in cancer cells so division never stops
how do cancer cells induce angiogenesis
tumour cells release proangiogenic factors (VEGF)
endothelial cells secrete mmp to digest tumour extracellular matrix
endothelial cells form a new aberrant blood vessel in the tumour
- disorganised, leads to hypoxic and normoxic environments
how do cancer cells cause invasion and metastasis
- proteolytic degradation helps cancer cells break off (E-cadherin)
- macrophages secrete chemokines and tumours secrete factors to affect macrophage function
- pericytes secrete CXCL12 to cause migration
- cells can die, become dormant or migrate to new tissues
what are the emerging hallmarks of cancer
deregulating cellular energetics, genome instability and mutation, avoiding immune destruction, tumour promoting inflammation
how do cancer cells deregulate cellular energetics
convert glucose to lactate irrespective of the presence of oxygen
how do cancers avoid immune destruction
- stop MHC processing to prevent the loading of antigenic peptides to MHC
- upregulated PDL-1 to inhibit T cells
- release cytokines to cause immunosuppression
how do tumour cells promote inflammation
- they release chemotactic factors to attract monocytes which differentiate into macrophages (TAM - tumour associated macrophages)
- TAMs release angiogenic factors, metalloproteases and mitogenic factors
incidence of cancer
approx. 1000 new cases daily, 450 deaths daily, 50% survival
incidence and risk factors of lung cancer
- 3rd most common in UK
- age/gender, smoking, gas exposure and cancer history
screening and treatment of lung cancer
- screening smokers aged 55-74
- treat with chemo, radio, surgery or chemo radio
