Lecture 9 Flashcards
What is SAGE?
Serial analysis of gene expression - counts transcripts and compare gene expression between cell types of tissues
Outline SAGE
- Isolate mRNA and convert to cDNA
- Cut transcript with anchoring enzyme
- Release bp tags using tagging enzyme
- Ligate into plasmids for sequencing
- Count tags to estimate relative gene expression
What is replacing SAGE?
Whole RNA sequencing
What are the limitations in SAGE?
- Only transcript levels; not variants
- Homologies with other genes
- May not be in 3’ end where SAGE acts
What are three types of diagnostic method?
What are the advantages and disadvangtages of each?
- Biopsy- Cheap but can be invasive and may increase risk of metastasis
- Non-invasive imaging, e.g. MRI/CT - Accurate and sensitive, non-invasive but is expensive
- Molecular markers - Sensitive and can be non-invasive but is not available for all cancers
What could biomarkers be used for?
- Detecting presence of disease
- Detecting severity of the disease
- Predict response to treatment
- Monitore response to treatment
- Detect reccurence of disease
How do traditional cnacer drugs disrupt DNA replication or cell division?
- Nucleotide analogues
- Nucleotide synthesis disrupters
- Topisomerase inhibitors
- DNA-binding drugs
- DNA-cross linkers
- Intercalatin agents
- Inhibitors of mitosis
How are the traditional cancer drugs seen as selective?
Target according to proliferation rate - which is much higher in cancer cells than in the rest of the body
What are biologicals?
Treatments which use bodies natural substances to treat cancer. e.g.
- Hormones and hormone disrupters
- Receptor blockers
- Immunostimulators
- Targeted toxins
- Gene therapies
- RNAi
What is immunotherapy?
Boosting the immune response to kill cancer cells
What types of immunotherapy exist?
- Molecules which are produced as part of immune response made in the lab
- Vaccinations against cancer cells to train immune system
- Therapeutic monoclonal antibodies that recognise molecules on the outside of cancer cells
What is the goal of personalised medicine?
What muts be considered?
Treatment to match each individual patient
- Is the gene a tumour supressor/tumour promoter
- Cell surface or intracellular
- Circulating or solid tumour
- Chemistry of treatment agent
- Delivery of the treatment?
What is the aim of checkpoint inhibition treatment?
Cancer cells have commonly lost p53 dependent repair and are dependent on DDR. By knockin our DDR in these cells the cancer cells cannot repair damage to DNA and hence traditional treatments, such as chemo, will be very effective on them. Whilst healthy cells will still have p53 repair and hence unaffected
What drugs have been developed for checkpoint inhibition?
- Chk1 and Chk2 inhibitors
- Pi3 Kinase inhibitors
- PARP inhibitors
What drug has been shown to extend life of breast cancer patients?
What does it target?
Herceptin
Internalisation of Her2