Hallmarks of cancer Flashcards
(47 cards)
What are the 6 hallmarks of cancer?
- Sustained proliferative signalling
- Evade growth suppression signals
- Resist apoptosis
- Activate invasion and metastasis
- Enable replicative immortality
- Induce angiogenesis
How many individuals are affected by new cases of cancer?
450 per 100 000
What is the mortality rate associated with new cases of cancer?
160 per 100 000
How do cancer cells achieve sustained proliferative signalling? (4)
- Upregulate and release their own mitogenic signalling molecules
- Stimulate neighbouring tissues to release growth factors
- Become more sensitive to growth factors to rapidly proliferate in the presence of normal mitogenic signalling
- Mutations can cause constitutive activation of growth factor-activated signal transduction
What is an example of sustained proliferative signalling? (2)
- Upregulation and overexpression of Her2 on breast cancer cells caused by HER2 gene amplification
- Gives cancer cells greater sensitivity to Human Epidermal Growth Factor
What is Her2? (2)
- Human Epidermal Growth Factor Receptor
- Receptor tyrosine kinase which signals via Ras to cause cell cycle progression, proliferation and enhanced survival
Which chromosome is the HER2 gene located on?
Chromosome 17
How is Her2 positive breast cancer treated?
Monoclonal antibody Herceptin which binds to Her2 receptor and prevents ligand binding and receptor dimerisation
How is Her2 positive breast cancer diagnosed? (3)
- Amplification status is graded into 4 categories
- Her2 amplification must be over a certain threshold to be prescribed Herceptin
- Borderline cases are sent for further cytogenomic analysis by FISH
How do cancer cells evade growth suppressors? (4)
Loss of function of tumour suppressor genes via:
- Inactivating mutation
- Transcriptional suppression via methylation of a promoter region
- Deletion via chromosomal abnormality
- Altered expression of tumour suppressor regulators
What are examples of tumour suppressor inactivation in cancer? (3)
- TP53
- RB
- Other mechanisms of growth suppression evasion include loss of cell-cell contact inhibition
How does RB work? (3)
- RB = retinoblastoma
- RB function is impaired in most cancers
- RB forms a complex with E2F which downregulates transcription of genes involved in cell cycle progression
What are the 2 groups of apoptotic regulators?
- Process extracellular signals (extrinsic pathway)
- Process intracellular signals (intrinsic pathway)
What are apoptotic regulators?
Genes involved in sensing apoptotic signals
What are apoptotic triggers?
Genes that convey signals from the regulators to the apoptotic effectors
What are the 2 groups of apoptotic triggers?
- Pro-apoptotic triggers (tumour suppressors)
- Anti-apoptotic triggers (oncogenes)
What is an example of apoptotic triggers?
Bcl2 protein family
What is the function of apoptotic triggers?
Regulate the apoptotic effectors (caspases)
How often is TP53 mutated in cancer?
In around 50% of all cancers
What is the function of p53?
Promotes cell cycle arrest to allow for DNA repair and/or apoptosis if repair is not possible
What is an example of a pro-apoptotic trigger (tumour suppressor)?
TP53
What is an example of an anti-apoptotic trigger (oncogene)?
BCL2
What is the prognosis of TP53 loss?
- Poor prognosis
- Loss of TP53 is a marker of MDS progression into acute myeloid leukaemia
How can BCL2 be overactivated in cancer? (2)
- Chromosome structural rearrangement resulting in coupling of BCL2 gene to IGH promoter region resulting in BCL2 overexpression
- Abnormality is frequently diagnostic of B-cell neoplasms (lymphoma)
