IBCD 2016 - Innovation and biomarkers in cancer drug development
Innovative imaging techinques to visualise drug targets
Prof Guus van Dongen - VU University Medical Center, Amsterdam, Netherlands
When I started this antibody development more and more the question came up when is an antibody effective and when not. So there were a lot of questions, what’s doing such a drug in the body and it was unpredictable when it became effective, yes or no. So it made me realise that the presence of a target and availability of a drug is not enough to explain efficacy and you should have more information what’s going on in the body. That made me decide to label all the targeted drugs, we call it magic bullets, we call it targeted drugs, we call it smart drugs, but are they really so fantastic as we assume? Indeed, what we experienced in our efforts with radio labelled drugs is indeed that they don’t always do what they are promised to do. So for better understanding and better sorting out the real promising drugs with the less promising drugs I think we need such objective information of what’s going on in the body with these drugs.
What follows radio labelling?
Actually we attach a minor amount of radioactivity to the drug, we do that in an inert way so the properties of the drug shouldn’t change. We are really tracking the drug after injection with a PET camera so you can really follow, you can quantitate, you can see where it is going to the tumour, you can see where it accumulates in normal tissue so that you can anticipate toxicity and you can quantitate, which is apparent. So for really optimising drug targeting, targeting to the tumour, that’s important information.
Once a drug accumulates in the tumour there’s no guarantee that it is effective, there can be resistance mechanisms. But it’s a first requirement for most of the drugs that they accumulate a sufficient amount in the tumour and even many of the approved drugs are not qualified in all cases to do that.
Were there any drugs that gave you surprising results?
No, actually you recognised the better targeting drugs and the poorly targeting drugs and indeed some drugs are quite predictable that they are good targeting and there we also find biomarkers that say something about the possibility of efficacy. But some drugs are much more unpredictable, especially small molecule inhibitory drugs like tyrosine kinase inhibitors. It’s much less predictable after injection what they will do in individual patients.
Do you think we will see a change in how these drugs are treated?
I’m a little bit sceptical, I more believe in biologicals, antibodies, they are more specific, have higher affinity. Also from the chemical point of view when you compare the chemical structures of those tyrosine kinase inhibitors they are looking quite similar, let’s again be specific, already it’s difficult to believe it has to compete with normal biological available ligands like ATP and sometimes that’s really formed in an appropriate way with certain tyrosine kinase inhibitors but others are weak inhibitors. So maybe they temporarily inhibit the process but after that they are losing activity or they are actually bypassing of other pathways. I’m not a strong believer in tyrosine kinase inhibitors.
There are also here a few best practice examples and I think we have to understand why specifically these tyrosine kinase inhibitors are effective and others not, the same as biologicals and the same also with immune checkpoint inhibitors. Now we have to understand why in certain patients they are tremendously effective and in others not at all. Exactly at this field we try to understand by image information whether we can get crucial information that can steer further drug development and selection.
I think what happened, we had the Human Genome Project then we learned about the normal DNA structure and the diseased DNA structure in tumours and then we were very optimistic. The pharma industry started massive development of drugs, most of the companies in the same direction, same screening procedures, they all came with similar types of products. Now we especially have to look what the distinguished properties are of drugs, what are really the game changers and why. Can we understand? Can we build based on that? But that’s my personal view.
How do you feel about the conference this year?
I think it was a very stimulating conference, indeed where the different came together. Yes, sometimes it can be provocative and that’s good, anyhow, to be critical about your own directions and to have a look back, also, what we did in the past and what did we achieve and what are the prospects for the future, of course.
