Targeted Therapy Flashcards
What are the benefits of targeted therapies?
ID within an individual all the mutations in the cancer they have, then use this information to:
- Improved diagnosis
- Reducing serious side effects
- Reducing use ineffective drugs
- Improving patient survival
- Improving quality of life
- Reduce costs
What are the best therapeutic targets for cancer cells? [1]
What is the next best target? [1]
Best therapeutic targets are found in cancer cells but not in normal cells e.g. gene product from a translocation
When there are more targets in cancer cells than normal cells (e.g. gene amplification: overexpression of HER2 or EGFR)
Name a drug that targets EGRF mutation [2]
Gefitinib or erlotinib
Tyrosine kinase receptors:
Name 4 key antibody targets that are GF receptors and / ligands
Epidermal growth factor receptor (EGFR)
HER2 (no ligand)
HER2/3 (ligand: HER2 can bind to HER3 – activates different pathway)
Vascular endothelial growth factor (VEGF)
Name two key intracellular growth pathways [2]
MAPK and PI3Kinase
State the results of switching of receptor / kinase activity of t
MAPK kinase
MAPK Pathway:
- Less proliferation
PI3Kinase:
* Less cell growth
* Less proliferation
* Less angiogenesis
raS
State the two main approaches for targeted therapies [2]
Antibodies
Small molecules tyrosine kinase inhibitors
State difference in antibody and small molecule kinase inhibitors
Antibodies:
* high selectivity
* targets are often restricted to the cell surface
* require intravenous or subcutaneous dosing because of their large molecular weight
* Can be conjugated to cytoxic drugs
Small molecule kinase inhibitors:
* vary in selectivity
* Oral
* Bind- ATP binding sites
* Can potentially bind a wider range of extracellular and intracellular targets (> one kinase)
Describe the mechanism of antibodies [2] and SMKI [1]
Antibody:
* Produce antibodies that target extracellular part of tyrosine kinase receptor
* Inhibits ligand binding or causes the ligand to bind in an area that doesn’t cause dimerization
SMKI:
* Binds to ATP binding pocket & intracellular-P cant occur
State the overall three mechanisms of monoclonal antibodies [3]
Killing tumour cell directly
Killing tumour cells via an immune-mediated mechanism
Vascular or stromal ablation: VEGF antagonsim
Monoclonal antibodies and cancer therapy mechanisms:
Explain how killing tumour cells directly via monoclonal antibodies works [4]
- Inhibit ligand binding
- Or possible delivery of toxic payload
- Signalling blocked
- Apoptosis induced
Monoclonal antibodies and cancer therapy mechanisms:
Explain how killing tumour cells directly via an immune-mediated mechanism works [3]
- Induction of phagocytosis
- Complement-dependent cytotoxicity (CDC)
- Antibody-dependent cell cytotoxicity (ADCC)
Monoclonal antibodies and cancer therapy mechanisms:
Explain how killing tumour cells directly via vascular or stromal ablation works [1]
VEGF antagonism
What are the two components of Trastuzumab emtansine (Kadcycla)? [2]
Herceptin (acts as the transporter)
AND
Anti-microtubule agent: DM1
Describe mechansim of trastuzumab emtansine (Kadcycla)?
Kadycycla is formed from the conjugate binding of Herceptin with DM1, which is an anti-microtubule agent
Drug is taken up by lysosome.
Within the lysosome: herceptin and DM1 dissociate and are released into cell
DM1 attacks cell tubule
This rash comes from which cancer drug? [1]
Trastuzumab - rash
