Genetic Alterations & Targeted Therapies Flashcards
(33 cards)
What is the intrinsic mechanism for p53 mediated apoptosis
BAX, NOXA and PUMA
= activation of cytochrome C
What is the extrinsic pathway of p53 mediated apoptosis
DR5/TRAILR2 and FAS
= activates caspases
What are the different manifestations of apoptosis
Nuclear fragmentation
Cell surface markers
Caspase catalytic activity
Cleavage of target proteins
What is one of the earliest indications of apoptosis
Translocation of the membrane phosphatidylserine from the inner to the outer plasma membrane
How can flow cytometry be used to investigate apoptosis
See the relative proportion int the different cell phases and the amount undergoing apoptosis
What stain binds to the phosphotidyl residues
Annexin 5
What is BAX
BCL2 associated protein
Ratio of BAX:BCL2 determines survival or death
Leads to cytochrome C release
What is PUMA
A BCL2 binding component 3
What is PIG3
Implicated in regeneration of ROS
What is TRAILR2
Cell surface transmembrane protein that mediates apoptosis
What is cytochrome C
Small heme protein component
Initiates apoptosis by activating caspases
What are the clinical consequences of p53 inactivation
Loss of cell cycle arrest in response to DNA damage
Prevention of p53-dependent apoptosis
= acceleration of tumour progression + cells resistant to treatment
What is autophagy
Another way of cell death
Cell degrades its own enzymes
Describe senescence
Cell remains alive but does not undergo division
Describe the steps of the Vogelstein Model for colorectal cancer
- Mutation or loss of FAP in 5q = hyperprolif. epthelium
- DNA hypomethylation = early adenoma
- Mutation in K-RAS in 12p = intermediate adenoma
- Loss of DCC? In 18q = late adenoma
- Loss of p53 in 17p = carcinoma
- Other alteration = metastasis
What does the Vogelstein Model depict
A series of mutation that occur n the progression from normal cells to colorectal cancer
And how the mutation are associated with histological features
What is Cetuximab
EGFR targeted antibody used in advanced colorectal cancer
In what tumours would cetuximab be ineffective
In RAS mutant tumours
How can prognostic and predictive bio markers be used to treat cancers
Allow stratified treatment
Better tailoring of therapies to the individual
Disease monitoring during treatment
What bio markers can be used in treatments
MYCN in neuroblastoma
HER2 in breast cancer
How can tumour informed liquid biopsies (TILBs) be useful
DNA sequences analysis of a patients tumour tissue sample using genome-wide sequencing
= minimally invasive monitoring of disease
Name a few novel therapeutic targets
Antibody targeting
Gene therapy
Small molecule inhibitors of oncogenes and associated growth signal transduction
What are the properties of an ideal target
Casual link with the transformed phenotype
Tumour specificity
Bio markers available for monitoring
Functional assays can be designed
Describe the Philadelphia (Ph) translocation in CML and ALL
Juxtaposition of BCR and ABL gene sequence
= chimeric fusion protein Bcr-Abl
