Cancer Flashcards
What is the definition of cancer?
Uncontrolled cell growth
What are the main environmental risk factors?
Sunlight - UV light
Radiation
Chemical
Viruses
What are the main lifestyle risk factors?
Diet
Smoking
Exercise
What is the biggest risk factor?
Age
What is chromothripsis?
‘Chromosome shattering’
High numbers of rearrangements in localised region
What is DNA stress?
Inefficient replication that leads to the replication fork slowing, stalling and / or breakage
When does DNA stress arise?
Increase in causes of replication fork defects
Defects in processing / response pathways
What do proto-oncogenes do?
Regulate various aspects of cell growth and division
How are tumour suppressor genes characterised?
Gatekeepers: regulate cell proliferation
Caretakers: act to prevent genomic instability
What is the DNA damage response?
Signalling pathways that act to prevent genomically unstable cells from continuing to proliferate
What is senescence?
Permanent cell cycle arrest
What are the main repair pathways?
Base-excision repair
Nucleotide-excision repair
Recombinational repair
Mismatch repair
How does non homologous end joining work?
KU70/80 protects double strand break ends
DNA-PKcs - process ends if required to remove damaged DNA components
Ligation of two broken ends back together
How does homology-directed repair work?
Uses homologous template (sister chromatin preferably)
Occurs in S and G2/M phase
What happens to the DNA damage response in cancerous cells?
It’s switched off. Permits growth despite high DNA damage and genomic instability levels
What are the functions of BRCA1?
Double strand break repair DNA replication stress response Chromatin modification Transcription regulation Cell cycle checkpoints Tumour suppressor (caretaker and gatekeeper)
What are the functions of BRCA2?
Double strand break repair
DNA replication stress response
Tumour supressor
What are the steps of colorectal cancer?
Normal cell -> Hyperpoliferation -> Adenoma -> Carcinoma
Mutations in what areas can lead to colorectal cancer?
APC gene mutation
K-ras mutation
DDC gene mutation
P53 mutation
How do somatic mutations vary within the same cancer type?
Different cancers are different in many ways - mutation types and genes involved.
Same tumour in different people vary
Pattern of mutation accumulation vary
Inter-tumour heterogeneity
How is cancer therapy a paradox?
Inducing DNA damage and replication stress is often a mechanism of cancer cell death during therapy
How does personalised therapy work?
Tailor therapies to genotype of patient and . or tumour
Genotype normal tissue for comparison
Genotype after treatment and adjust therapy to combat newly evolved clones
