Transcripts
DR. LINGWOOD:
So it turns out that the pump that is
responsible for drug resistance actually is
involved in the mechanism of Gb3 synthesis. And
what it does is it pumps a precursor for Gb3,
which is made on the outside of the Golgi here.
And if it flips it from the outside into the
lumen of these vesicles where the enzymes for
production of Gb3 are contained. So it
increases the precursor and you get an elevated
concentration of Gb3.
And what is very exciting is
that it's particularly the short chain Gb3
isoform that's elevated. So this is the form
that from the cell surface with VT and targets
it to the nucleus and generates high sensitivity
to verotoxin.
So verotoxin is a potential
anticancer agent. And I told you that verotoxin
will cause HUS, definitely, in baboons. But the
anticancer effects are at doses which have no
pathological effect. In animal models such doses
have given complete cancer elimination.
