small molecule signalling pathways Flashcards
what are the 5 types of inhibitors involved in small molecule signalling pathways
- tyrosine kinase inhibitors
- epigenetic inhibitors
- BLC2 inhibitors
- proteasome inhibitors
- PARP inhibitors
what happens in pathways with tyrosine kinase inhibitors
the pathway normally involves a ligand binding which stimulates growth. When the ligand binds it hyperactivates the pathway which causes uncontrolled growth. Normally result of a mutation
what are the functions of epigenetic inhibitors
- histone deacetylation
2. histone methyltransferase
what is chronic myelogenous leukaemia, and how are epigenetic inhibitors used in treatment
CML is a chronic malignant bone cancer caused by a chromosomal translocation fusing BCR-ABL. The fusion forms a fusion protein which hyperactivates ABL-kinase.
The treatment is called Imatinib. Imatinib competes with ATP to bind to the ABL-kinase. The competition stops phosphorylation at the effector molecules
how are the effects of Gleevec used to treat GI stomal tumours
- dramatic effect in the treatment
2. resistance develops after 2 years
why is using multiple inhibitors in combination the most effective way to treat cancer
because tumours normally have more than one mutation.
where can mutations occur in tumours
- binding site on the receptor
- oncogene signalling
- pathway mutations
what is the main function of BCL2 inhibitors
controls apoptosis
what are the two pathways of BCL2 inhibitors, describe these two pathways
- intrinsic: controls apoptosis by the BCL2 family which are pro and post apoptic. They control the way mitochondria sense what is happening
- extrinsic: binding to caspase receptors directly, binding activates caspases which causes apoptosis
what is the function of proteasome inhibitors
block the ubiquitin-proteosome pathway which is responsible for proteins degradation and production of a growth-promoting pathway
PARP inhibitors are used in what types of cancers
- familial breast
2. ovarian
what are PARP inhibitors
the pathway in which cells use enzyme pathways to repair DNA damage activated by cancer therapy. this pathway is deregulated during cancer, it is possible to activate therapeutically.
describe the concept of “bracness”
this is where some sporadic tumours share traits with those carrying the BRAC1/2 mutation, therefore they share defects in homologous DNA strand repair.
bracness identifies people who might be more successful on PARP inhibitors because they have an underlying mutation
what is the treatment for non-small cell lung cancers
Gefitinib
patients who show little treatment to chemo tend to react well to gefitinib. They also normally carry a mutation EGRF gene. A rash is a positive indicator that the drug is working.
