biology of cancer Flashcards
what mutation are hereditary cancer usually associated with?
- mutation in tumour suppressor gene
what is retoblastoma?
- rare childhood cancer familial form (40%) and sporadic form (60%)
- familial form affects younger children and is often bilateral
- sporadic form is unilateral
- tumour caused by mutations in Rb tumour suppressor gene
what is the mutation in retinoblastoma and what is the effect?
Rb gene encodes retinoblastoma protein pRb
regulates cell cycle progression
inhibits transcription of cell cycle proteins by binding to the transcription factor E2F
in the absence of functional pRb, cell cycle progression uncontrolled
what are 2 genes that predispose to breast cancer?
- BRACA1 and BRACA2
- they are large nuclear proteins that repair DNA double strand breaks
cells deficient in either protein show “genomic instability”
how is risk of breast cancer categorised?
low risk = population risk
less than 3% aged 40 - 50
lifetime risk less than 17%
moderate risk:
3-8% aged 40 - 50
lifetime risk 17-30%
high risk:
greater than 8% aged 40 - 50
lifetime risk greater than 30%
how are different risk groups monitored for breast cancer?
low risk = population risk
mammographic screening from age 50
breast awareness, lifestyle information
moderate risk:
- age <40: information, counselling
- age 40-49: annual mammography
high risk:
- refer to specialist clinic, genetic counselling
- genetic testing IF affected family member agrees
which family history factors are considered high risk for breast cancer?
two relatives with BrCa < 50 yrs
three relatives with BrCa < 60 yrs
four relatives with BrCa any age
ovarian cancer + BrCa < 50
bilateral BrCa < 50
male BrCa + BrCa < 50
Jewish ancestry
multiple cancers at young age
which chemotherapy agents are most useful for treating braca1/2 deficient tumours?
- cisplatin
- PRAP
drugs induce DNA damage that is repaired by BRCA1 and BRCA2
describe how PARP inhibitors can be used to induce synthetic lethality in tumour cells?
BRACA usually acts to repair DNA so cells can survive
if there is no BRACA being expressed then PARP can repair DNA and the cell will still survive
PARP inhibitors will result in no mechanism of repair for those without BRACA gene expression- so it will lead to tumour cell death
what is the targeted therapy for CML?
- imatinib
- competitively binds the kinase domain of BcrAbl so tumour cells cannot proliferate
