MCB Lecture 29 Cancer treatment Flashcards
Describe what is meant by targeted therapy
Only the mutated driver is targeted. Thus, normal versions are not adversely affected
What are the two standard therapeutic approaches?
- Block cofactor site of an enzyme
2. Antibody binds to the receptor, or to the ligand so that there can be no intracellular response
Describe therapy in CML
CML is caused by bra-abl on Philadelphia chromosome
This codes for a constitutive lay active tyrosine kinase, which activates STAT5
STAT5 leads to proliferation of hematopoetic cells
By blocking the ATP binding site in the tyrosine kinase, we don’t get phosphorylated STAT5, and thus no proliferation
What does Imatinib do?
Imatinib blocks the ATP site in the brc-abl tyrosine kinase
Describe how genetics is important in targeted therapy
Not all forms of the cancer will have the same mutations
We need to do genetic screens to see if a person has a mutation to see if the targeted therapy will be any help
Describe therapy in melanoma
Half of melanomas have a mutation in BRAF
By targeting BRAF, we stop the pathway that leads to cell growth and proliferation
What does vemurafenib do?
Vermurafenib blocks the mutated form of BRAF, thus preventing cell proliferation
Describe the problem of acquired resistance
Compounds further down the pathway mutate, and thus we get tumour growth again
Describe the change in survival time with targeted therapies
Targeted therapies increase the survival time
However, after a certain amount of time, the cancer comes back and the patient dies
What is being done to improve acquired resistance
Compound treatments: target all the drivers at once so there can be no evolution of resistance
Describe why personal genomics is important for cancer treatment
This is because we need to see which particular mutations an individual has so that we get them the best treatment
Explain gene therapy
Recombinant DNA put into a patient (virus, vector) to replace the mutated or defective DNA
This has n,y had marginal success
