Yep, that's the long and the short of it. CLTX correlates with...

Yep, that's the long and the short of it. CLTX correlates with MMP-2 expression at the tissue and cell level (so MMP-2 definitely seems to be involved), but at the higher resolution sub-cellular level labelled CLTX and MMP-2 do not precisely co-locate, suggesting MMP-2 is not the direct ligand. What I think they are suggesting in the abstract is that the ligand is another component or components of a receptor complex that also contains/involves MMP-2 and that, after the initial binding event, CLTX and its ligand are redistributed which results in the diffuse but loosely associated (not random) staining pattern.

In the emerging era of precision medicine, it is becoming increasingly important to understand the molecular target and mechanism of action of your drug. This has practical benefits in that you can stratify your clinical trial participants to only contain people expressing your target (and sometimes the right variant of the target) which will result in the highest possible efficacy stats by excluding non-responders. This then results in a drug that is approved for a targeted patient population - think therapeutics targeting HER-2+ breast cancer.

MMP-2+ status is currently being used for stratification in our trials which seems a reasonable proxy as, although it is not the direct ligand, it appears strongly correlated with binding. Having said that, it will still be desirable to identify the direct ligand to bring greater understanding of the mechanism of action and therefore greater granularity to patient stratification and use in other cancers.

With MMP-2 status being used for stratification, I was particularly interested in the proportion of glioblastomas that are MMP-2+ (ie the proportion of tumours that are addressable by this therapy). A cursory lit search suggests 73% of treatment-naive tumours are MMP-2+ - I'm wondering if the proportion is higher in recurrent tumours. MMP-2+ status is also a negative factor for prognosis and overall survival making treatment for this patient group even more important.

I'd love to see the presentations at SNO...