Cancer Biology Flashcards
(43 cards)
What are the 6 Hallmarks of Cancer?
Activating invasion and metastasis, Sustaining proliferative cell signalling, Resisting cell death, Evading growth suppressors, Enabling replicative immortality, Inducing angiogenesis
What is a proto-oncogene?
A gene that is responsible for normal cell growth.
Name some proto-oncogenes.
Ras, B-Raf, EGFR, c-MET, tyrosine kinase
What occurs to the Ras proto-oncogene for it to mutate into an oncogene?
There is a point mutation from Glycine to Valine.
What happens as a result of a Ras mutation?
Constant signalling without growth factor, no ligand binding leads to overexpression of proteins, this is known as sustained proliferative signalling.
Describe the direct mechanism of viral oncogenesis.
The virus acts from within the cell to form a tumour. The viral genome can form an episome, or can integrate itself into the genomic DNA. These lead to viral oncogene expression, which leads to rapid cell growth and cancer.
Describe the indirect mechanism of viral oncogenesis.
The virus acts from outside the cell to form a tumour. The two ways this can happen are: the virus can trigger chronic inflammation and persistently cause oxidative stress to local tissue, or it can produce immunosuppression which dulls anti-tumour mechanisms.
What viruses can cause oncogenesis?
HBV, EBV, HPV, HIV, herpes virus
What common mutations in EGFR signal transduction pathways can cause cancer?
EGFR mutation, Ras mutations, B-Raf mutations, EGFR overexpression, EGFR extracellular and intracellular domain mutations, EGFR cytoplasmic domain mutations
How does Trastuzumab work?
It binds to HER2 receptors (TRK), which are overexpressed in some breast cancers, which in turn causes an inhibition of the MAPK and PI3K signalling cascade leading to cell cycle arrest. It also attracts immune cells like NK cells to tumour sites.
What is the biomarker for CML?
BCR-ABL gene translocation
What is the biomarker for BRCA 1/2 breast cancer?
BRCA 1/2 gene mutations
What is the biomarker for HER2 breast cancer?
HER2 gene amplification
What is a biomarker for NSCLC?
EGFR kinase domain mutation
What is the BCR-ABL oncogene also known as?
The Philadelphia chromosome
What does BCR stand for?
Break-point cluster region
What does ABL refer to?
It is a protein tyrosine kinase that is involved in cell differentiation, adhesion and growth.
Why does the BCR-ABL cause cancer?
It mimics growth factors. It will bind to an RTK leading to RAS and PI3K/AKT activation. The phosphorylation of Tyr177 in the BCR section leads to activation of this pathway by interacting with the SH2 domain in GRB2.
What drug is indicated to treat BCR-ABL initiated cancer, and how does it work?
Imatinib is used for CML caused by BCR-ABL translocation. It binds to intracellular pockets in RTKs and inhibits ATP which prevents phosphorylation, activation of GFR and downstream signalling.
Name the important tumour suppressor genes.
p53, retinoblastoma, cyclin dependant kinases, cyclin, cyclin dependant kinase inhibitors
What are cyclins/cyclin dependant kinases/cyclin dependant kinase inhibitors?
They are complexes that control different parts of the cell cycle. A CDK will bind to a cyclin to cause activation. The inhibitors will then in turn switch this off to slow the cell cycle down.
What is retinoblastoma?
A protein that acts as a ‘brake’ in G1. It inhibits the genes necessary for progression into the S phase. Phosphorylation of this protein will release the E2F transcription factor which activates the transcription of genes that encode proteins for S phase.
What is a sporadic cancer?
One that has no known cause
What is a familial cancer?
A cancer that is caused by combination of genetic and environmental factors. There is no particular pattern however.
