Early effect of PI3K-Akt-mTOR blockade on in vitro 18F-FDG uptake in HER2 breast cancer resistant to trastuzumab

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Published: 15 May 2013
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Dr Yanina Dockx - University of Antwerp, Edegem, Belgium

ecancer reporter Peter Goodwin talks to Dr Yanina Dockx at the 2013 IMPAKT meeting in Brussels.

Aberrant activation of the PI3K-Akt-mTOR pathway is an important driver of resistance to HER2 targeted therapies and is involved in glucose homeostasis. 18F-FDG-PET has been proposed for early response assessment for targeted therapies, but knowledge on the effects of blocking this pathway on FDG uptake dynamics is limited.

The study investigated the effect of pharmacological PI3K-Akt-mTOR blockade on in vitro FDG uptake in HER2 breast cancer cells resistant to trastuzumab.

Blockade of PI3K-Akt-mTOR in trastuzumab resistant HER2 breast cancer was found to affect in vitro 18F-FDG uptake in transient and opposite ways, depending on the pharmacological target and duration of treatment.

Therefore, further validation is necessary to elucidate the cellular mechanisms involved in tracer uptake prior to routine clinical use for early response assessment.


ecancer's filming at IMPAKT has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

IMPAKT Breast Cancer Conference 2013

Early effect of PI3K-AKT-mTOR blockade on in vitro 18F-FDG uptake in HER2 breast cancer resistant to trastuzumab

Dr Yanina Dockx - University of Antwerp, Edegem, Belgium

Yanina, we’ve heard a lot about targets and biomarkers and especially when these biomarkers could be targets for therapy. You’ve been doing exactly that in your in vitro study, can you tell me what you were trying to do?

I’m looking for a biomarker to check the early effects of targeted therapies. The biomarker that I’m using in an FDG, it’s a tracer for PET scans, and then I look at three different drugs used for targeting a specific pathway really frequently activated in breast cancers, that’s the PI3K-AKT-mTOR pathway. I’m looking at trastuzumab for HER2 antagonists, PI3K inhibitors and mTOR inhibitors and I’m looking for the effect of FDG, if it can predict the early effect of these treatments.

So you’ve tried looking at each one for the blockade individually, first of all, what happened and what did you see in vitro?

That was very interesting indeed. We see different kinds of effects on the FDG with the three different drugs so that is actually going towards really targeting therapy, that every single targeted therapy has its own biomarker. So, for instance, we have seen that FDG is a very good biomarker for the PI3K inhibitors but that we see actually an under- and over-estimation with the two other drugs. Apparently other mechanisms like negative feedback loops or an uncoupling of the glucose metabolism and the proliferation is active with trastuzumab and everolimus.

What are you discovering by these experiments that could be practically valuable to doctors?

What I’m trying to do is actually when doctors give targeted therapy to patients, patients have side effects and only after a couple of cycles of these targeted therapies doctors can evaluate the response to these therapies. Now what I’m trying to do with FDG-PET is after one or two days looking if we can predict the response after a while. So, for instance, if a patient is not responding to a therapy then I can say after two days it’s not working, we have to switch to another one. So the patient isn’t actually suffering from the side effects and we can switch to another therapy more early in the beginning of the disease progression.

And how much time do you think you could save and how much in the way of side effects, unnecessary treatment, do you think you might spare the patient?

Depending on the type of therapy but I would say two months. So just after one dose and then the next day we could do an FDG-PET or another tracer.

When you block more than one biomarker, though, the picture gets more complex. Have you anything to say about that?

Then we have to combine also the tracer because probably a targeted therapy has a specific tracer so we have to combine different tracers in one scan to see what kind of therapy is working and what not.

What do you foresee doctors doing with this kind of technology in the near future?

In the near future, it’s difficult to say. It’s going to take much longer than that but I think that FDG-PET is going to have an alternative for biopsies and have an earlier response possible for targeted therapies.

Could you tell me just a little bit more about what you do in FDG-PET, how does it work?

What I am actually doing is working on cells, so that’s in vitro work. It’s not really a PET scan like in humans but I use the PET tracer that is injected in humans, I add it to my cells and then I cultivate, like in humans, and then afterwards I take pictures of it and I count how much uptake there is, like in humans but then with specific cells.

So you get specific knowledge of functionality.

Yes, that’s true. That’s something that’s additional information instead. CT or MRI gives you just the images, anatomical images, and what PET gives you additionally is how it’s functioning. So if you have a tumour that is completely dead, so necrosis, you could see that on the PET images because it’s not active and you don’t see that on CT. So you can look in an early stage what the effect of the therapy is.

What kind of message would you like doctors to take away from this new area of development that you’ve been working on?

I hope they will follow the articles that we publish and have a broad view about molecular imaging because I think that’s what we will use in the future to get additional information besides the biopsy and other targets.

Is it telling you that, for instance, blocking more than one of these biomarkers could increasingly be feasible?

Yes, I think it would. It’s difficult to say now but I think in the future it will.

Thank you very much for joining us.

You’re welcome.