Flashcards in Aetiology of Cancer and Neoplasms II Deck (41):
What are selfish cells?
Cancer cells with selective advantage over normal regulated cells
What is difference with cancer cells to normal?
Large no. dividing
Large nuclei variable
Small cytoplasmic volume
Variation in cell size and shape
Loss of specialised cell features
Poorly defined boundary
What are doublings?
tumour cell mass doubling in size
What is Carcinogenesis?
Process of inducing cancer
What is a change to DNA called?
What are 6 hallmarks?
Resisting cell death
sustain proliferative signalling
Evading growth surpressors
Activate invasion and metastis
Enable replicative immortality
How do cancer cells sustain proliferative signalling?
Acquire mutations short circuit leading to unregulated growth
What is an e.g of sustaining proliferative signalling?
Mutation in Ras oncoprotein disrupts normal negative feedback
How do cancer cells evade growth suppressors?
Acquired mutations interfere with inhibitory pathways
What is an e.g of growth suppressor?
How do cancer cells resist cell death?
Evade apoptotic signals
What is an e.g of resisting cell death?
Dysregulation of anti-apoptotic BCL-2 family
How do cancer cells enable replicative immortality?
Cancer cells maintain the length of their telomeres
what is an e.g of replicative immortality?
Overexpression of telomerase
How do cancer cells induce Angiogenesis?
Growth of new blood vessels need for tumour survival and expansion
How do Cancer cells activate invasion and metastasis?
Move to other parts of body and start secondary tumours
How does cancer grow and spread?
Duplicate and invade surrounding tissue, produces TAFs and competes with normal tissue killing it for space some cells detach to create secondary tumour
What are the 4 metastatic steps?
Motility and invasion from primary site
Embolism and circulation in blood or lymph system
Arrest in a distant capillary
Extravasation into target organ
What external stimulus do tumour cells use to metastasize?
Tumour associated macrophages TAMS that supply cancer with EGF epidermal growth factor and CSF-1
What are 4 Enabling hallmarks?
Deregulating cellular energetics
Avoiding immune destruction
Genome instability and mutation
Tumour promoting inflammation
How does genome instability and mutation work?
Several chromosomal abnormalities drive tumour progression
What is an eg of genome instability?
defects in BRCA 1/2 in breast cancer
How does tumour promoting inflammation work?
Inflammatory cytokines promote tumour growth
What is an eg of tumour promoting inflammation?
How do cancer cells avoid immune destruction?
Invisible to bodys immune system -disable immune system and regulate Tregs and MDSCs
How do cancer cells deregulate cellular energetics?
Use abnormal metabolic pathways to generate energy - high rate of glycolysis
What is the Therapeutic target for Sustaining proliferative signalling?
What is the Therapeutic target for Evading growth surpressors?
Cyclin dependant kinase inhibitors
What is the Therapeutic target for Avoiding immune destruction?
Immune activating anti-CTLA4 mAb
What is the Therapeutic target for Enabling replicative immortality?
What is the Therapeutic target for Tumour promoting inflammation?
Selective anti-inflammatory drugs
What is the Therapeutic target for activating invasion and metastasis?
Inhibitors of HGF/c-Met
What is the Therapeutic target for inducing angiogenesis?
Inhibitors of VEGF signalling
What is the Therapeutic target for genome instability and mutation?
What is the Therapeutic target for Resisting cell death?
Proapoptotic BH3 mimetics
What is the Therapeutic target for Deregulating cellular energetics?
Aerobic glycolysis inhibitors
What 3 areas co-opt and form the Tumour stroma?
What is a chemical agent or radiation that causes cancer?
What are cancer causing genes called?
Where are oncogenes derived from?