Stratified medicine Flashcards
What is G6PD?
Glucose -6-phosphate dehydrogenase deficiency
X-linked recessive
Sensitivity to oxidative stress => causes haemolysis => jaundice
Common in Africa and Med
What is the advantage of G6PD?
immune to malaria
What main factor can influence a patient’s ability to metabolise a drug?
Genetics
- single-gene disorders, often encoding enzymes which degrade the drug
What genetic abnormality is linked to CML?
Philadelphia chromosome
translocation 9;22
=> BCR-ABL
Why are cancers so difficult to treat?
- multiple genetic defects
- difficult to target specifically
How does imatinib work?
Targets and inhibits BCR-ABL
BCR-ABL is an abnormal TK enzyme created by the mutation.
It is only present in cancer cells, and its inhibition leads to cell death.
What are examples of targeted treatments?
- imatinib = CML
- crizotinib = NSCLC
How can targeted therapies be picked for patients?
through pathology of biopsies
What is stratified medicine?
Stratified medicine is based on identifying subgroups of patients with distinct mechanisms of disease, or particular responses to treatments
How can new therapies be created?
targeted therapies designed to interfere in specific biologic processes
e.g. – Cloned proteins, monoclonal antibodies, RNA / DNA / viral vectors, hybrid molecules
– Rational molecular design of small molecules – chemistry and 3-D protein structure
– Immunomodulatory therapy, target bodies own immune defences to the tumour
How can we use stratified medicine in prediction?
- biomarkers for diagnosis, prognosis and therapeutic decisions
– Molecular diagnostics, the application of molecular pathology
e.g.
– ER, BCR-ABL, HER-2 , EGF-R, K-RAS, B-RAF, ALK, BRCA, CD20
What are the possible drawbacks to stratified medicine?
Common diseases are fragmenting
Small populations of available patients
Privacy and use of tumour samples / marker information
The target keeps moving
Can require large trials to find small population who benefit
