6. Targeted cancer therapies Flashcards
What are the best targets for cancer therapy?
Those found in cancer cells but not in normal cells
What are the second best targets for cancer therapy?
Where there are more of these targets in cancer cells compared to in normal cells e.g. an overamplification of a gene in cancer cells
What is the other type of target in cancer therapy that is least preferable?
Targets that are present in both cancer and normal cells but the normal cell will regenerate
What are targeted cancer therapies?
These are therapies that block the growth and the spread of cancer by interfering with specific molecules involved in tumour growth and progression
What is the target for breast cancer?
HER2 - this gene is amplified
What is the main treatment used to target breast cancer?
Trastuzumab
What are the two mechanisms of antibodies in cancer therapy?
Inhibitors of growth receptors - bind to the growth receptors and prevent growth signalling
OR
Antibody-drug conjugates - binds to the drug to the receptor that targets the tumour cells
How are tyrosine kinase inhibitors used for cancer therapy?
These are small molecule targeted therapy - bind to the tyrosine kinase receptors which are responsible for cellular division - so prevent the division from occurring
How can mAbs be modified to increase their efficacy?
Stable linker - releases the payload only in the target cell
Selective monoclonal antibody in the antigen binding region - high specificity
Potent cytotoxic payload - 100-1000 times more efficacious than regular chemotherapeutics
What is the mechanism of action of trastuzumab?
Prevents cleavage of the receptor
Inhibits dimerisation
Causes endocytosis of HER2 receptors - reducing the number of receptors present on the membrane
How do monoclonal antibodies work as a cancer therapy?
Kill the tumour cell directly
Kill the tumour cell via immune-mediated mechanism
Vascular or stromal ablation
How do antibodies access tumour cells?
The blood vessels of tumour cells are leaky (when normal cells should not be) and so large molecules have access to malignant tissue and there is no lymphatic drainage system so they remain here
What is the ending of a tyrosine kinase inhibitor?
-tinib
How might a cancer cell be resistant to tyrosine kinase inhibitors?
If there is a mutation in the tyrosine kinase receptor e.g. a deletion in the gene responsible
What are the side effects associated with targeted therapies?
Skin changes - rash, dry, itchy, alopecia
High blood pressure
Slow would healing and blood clotting
Congestive heart failure (HER2)
