L14 - rational treatment of cancer Flashcards
What are some examples of rational cancer treatment strategies?
Induce differentiation, discourage proliferative signalling, promote apop signalling, exploit checkpoint vulnerability, identify relevant population for specific strategy
How are gene expression arrays uses to stratify cancers?
Analyse g.e. in particular cancers and identify expression/downreg of particular genes associated with low survival - target these genes
What is one way of targetting acute pro-myelocytic leukaemia?
Exploit differentiation by treating with all trans retinoic acid or arsenic trioxide. Recruits ubiq ligase to destroy the fusion protein (normally it would force differentiation)
Why are tumour suppressor genes difficult to target?
They are not normally present - LOH
What is druggability?
Whether or not the target protein has a defined structure that specifically binds low molecular weight chemical entities
The structure a drug binds to is usually a cavity with what properties?
Vulnerable to low MW compounds that inhibit function of the cavity and disrupts catalytic activity
Provides lots of points of contact for drug - more potent and more specificity
What is an undruggable target?
TF oncogenes e.g. c-myc and fos
DNA binding cleft is similar between TF therefor not sufficiently specific
What are the pros and cons of kinases are cancer drug targets?
PROS - many are oncogenes - 518 in genome - very druggable (ATP sub binding cleft) CONS - many have same common ancestor - not sufficient variation that allows dev of specific inhibitors
How can we exploit checkpoint vulnerability?
Normal cells stop cc and initiate DNA repair when DNA is damaged. Cancer cells lack this machinery so they can’t repair the damage - this puts the cell at risk of mitotic catastrophes after a few rounds of replication
