Cancer I and II Flashcards
6 hallmarks of cancer
evading apoptosis
self-sufficiency in growth signals
insensitivity to anti-growth signals
sustained angiogenesis
limitless reproductive potential
tissue invasion and metastasis
example of how limitless replicative potential can emerge
acquisition of telomerase function, blocks to differentiation
example of a cancer which can emerge via a chromosomal translocation mutation
CML
examples of mutations which can cause cancer
chromosome instability, amplification or deletion of regions, base pair mutations
Kataegis
clustered nucleotide substitutions, a type of localised mutagenesis which can exist in cancer cells
Xeroderma pigmentosum
early onset skin cancer- hypersensitivity to UV light caused by mutations in nucleotide excision repair which allow error-free copying of thymidine dimers that can potentially cause cancer
lynch syndrome
condition leading to a high chance of developing early-onset colorectal cancer, issue with Mut proteins used in repair- these proteins recognise the distorted strand
BRCA gene
involved in the repair of DSBs using homologous recombination, which is more accurate than the alternative (NHEJ)- BRCA genes stimulate end resection and strand invasion
possible mechanism of oncogene induced replication stress
lack of dNTPs, histones, replication proteins etc leading to more fork stalling, DNA breaks etc- possibly leading to concentrations of mutations
most frequently mutated gene
p53
name of the technique used to determine where a cancer may have originated
mutational signature analysis
3 familial cancer syndromes and the mutations which cause them
Li-Fraumeni syndrome- p53
Retinoblastoma- Rb
Hereditary Breast and Ovarian Cancer (HBOC) syndrome- BRCA1/2
p53 function
transcription factor for genes like cyclin-CDK2
what normally keeps p53 levels low
interactions with ubiquitin ligase
Rb function
transcriptional repression- its mutation can therefore lead to overexpression of DNA replication genes
example of an oncogenic virus
RSV- leads to src being inserted into tge genome, potentially leading to cancer by displacement or mutation of important bits of the genome- can also spread cancer through packaging mutated DNA
Src
encodes a tyrosine kinase, involved in growth factor signalling
example of rational therapy in CML
inhibition of Bcr-Abl kinase that causes the expansion of cells with imatinib, preventing downstream regulation by these ongogenic kinases
rational therapy which inhibits growth factor receptors
herceptin- monoclonal antibody binding Her2, which is upregulated in breast cancer
example of rational therapy for BRCA mutant cells
PARP-targeted drugs, trapping these PARPs seems to lead to DSBs accumulating and the cells dying- e.g. olaparib
