Cancer Flashcards
What is cancer? (3)
Disease of malignant cell growth
Usually due to DNA damage in specific genes leading to aberrant signal transduction
Results in abnormal + uncontrolled cell proliferation
Why is cancer predominantly a disease of the elderly? (3)
Result from accumulation of mutations in certain gens
~4-8 required for cancer to develop
These accumulate over time
What are some causes of cancer? (5)
Genetic predisposition Immunosuppression Chemical exposure + smoking Radiation exposure Viruses e.g. EBV, HTLV-1
Which 3 types of genes are affected in order to cause cancer? (6)
Proto-oncogenes -> oncogens (e.g. BCL-ABL in CML)
Tumour suppressor genes (e.g. Tp53 which codes for p53)
- mutated supressor genes lose their ability to properly regulate cell division
Metastasis-promoting + -suppressing genes
Explain the role of Rb cell cycle reg? (4)
Rb is bound to E2F
@ G1/S checkpoint, Rb is phosphorylated
pRb detaches from E2F
E2F acts as a TF + upregulates cyclins + CDKs required for the next cell cycle checkpoint
Also upregulates enzymes needed for S phase
Explain the role of p53 in cell cycle reg? (6)
Activated upon DNA damage
Normally bound to Mdm2 but dissociates when there is DNA damage, hypoxia or cell cycle abnormalities
Causes cell cycle arrest allowing DNA to be repaired
If repaired cell cycle is resumed
If not, cell is programmed for apoptosis
Explain the process of metastasis (4)
Cell from primary tumour spread to 1st organ/tissue connected by lymph or blood (e.g. GI cancers spread to liver via hepatic circ)
Organ pref model - some tumours require certain environment e.g. certain GFs + so metastasise to certain organs (e.g. prostate to bone)
What therapies are available for cancer? (7)
Chemo (cytotoxic drug mix) Radiotherapy Stimulate tumour suppressors (Mdm2, p53) Block oncogens e.g. Gleevec for BCR-ABL gene Stimulate immune system Hormone therapy Anti-angiogenic drugs
Common carcinogens (4)
Chemical = cigarette smoke, coal tar Radiation = UV light, asbestos (structure) Viral = EBV Genetic = inherited predispositions (BRCA 1+2 mutations)
How do carcinogens promote cancer development? (3)
Carcinogens gents directly involved in causing cancer either by DNA damage or disruption of met. processes
Co-carcinogens promote activity of other carcinogens
Sources of radiation + how they promote cancer development? (7)
Background radiation is most common e.g. radon
Occupation exposure
Medical irradiation
Remnants of atomic weapons
High energy of ionising radiations disrupt chem bonds causing production of highly reactive radicals
React with nearby molecules + can cause DNA damage
Most ss breaks can be repaired normally, ds breaks are harder to repair
How does ataxia telangiectasia predispose an individual to cancer? (3)
Ataxia telangiectasia = defect in ATM gene
Responsible for cell response to dsDNA breaks
Ataxia, increased cancer risk, slowed rate of growth
How does xeroderma pigmentosum predispose individual to cancer? (4)
Defect in nucleotide excision repair (NER)
Defective DNA repair
DNA damage greatly increases after UV exposure
Severe sunburn, limited growth of hair, many freckles
How does Fanconi’s anaemia predispose an individual to cancer? (3)
Defect in proteins responsible for DNA repair
Most patients develope AML + BM failure by 40yrs
Congenital defect common, short stature
What viruses are associated with human cancer? (5)
DNA viruses - EBV (Burkitt's lymphoma) - HPV (cervical cancer) - HBV (hepatoma) RNA retroviruses - HTLV-1 (adult T-cell leukaemia lymphoma) - HIV (many cancers)
What properties are required of tumourigenic viruses? (3)
Stable association with cells (chromosomal integration)
Not kill cells
Evade immune surveillance
What is Knudson’s hypothesis for heriditary cancer? (4)
Only requires single ‘hit’ (mutation event) as first hit is inherited
Could be due to point mutations, gene conversion, deletions, BRCA1
First hit = loss of heterozygosity
Second hit = leads to loss of function
What is the function of proto-oncogenes? (3)
Stimulate growth
May be mutated -> oncogenes
Mutations causing cancer have a dominant phenotype (but rarely inherited as som. mutations)
Describe the life cycle of a retrovirus (6)
Enveloped viruses that replicate via reverse transcription
Bind to receptor on cell surface + fuse with membrane
Stimulates uncoating which releases +ve sense ssRNA into cysoplasm
Can produce DNA using its own reverse transcriptase enzyme
DNA integrated into host genome
Allows for transcription + translation of viral proteins
(assemble in cytoplasm + exit cell via exocytosis)
What chromosomal translocations are involved in Burkitt’s lymphoma and CML? (4)
Burkitt’s lymphoma = chr8 (MYC) + chr14 (Ig heavy chain) -> unreg expression of MYC
CML is due to Philadelphia chr (95% case) = translocation b/w chr9 (ABL) + chr22 (BCR) to create BCR-ABL oncogene
- enhances tyrosine kinase activity
Which therapies target oncogenes? (2)
Monoclonal Abs target surface receptor proteins on tumour cells:
- trastuzumab, cetuximab
Small molecule inhibitors (usually kinase inhibitors):
- Imatinib (BCR-ABL)
What is the function of tumour suppressor genes? (3)
Regulate cell cycle checkpoints, differentiation or DNA repair
What is β-Catenin? (4)
Protein that regualtes coordination of cell-cell adhesion + gene transcription
Can bind to APC + form degredation complex or to TPC promoting gene transcription
β-Catenin-APC complex is inhibited by Wnt
