Molecular profiling of primary compared to metastatic lesion in gynaecologic cancers

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Published: 31 Oct 2013
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Prof Helga Birgitte Salvesen - University of Bergen, Norway

Prof Helga Birgitte Salvesen talks to ecancer at the 2013 ESGO meeting in Liverpool about the molecular profiling of endometrial tumours. Prof Salvesen stresses that there is a need to increase the knowledge on what the key targets are for clinical trials. One potentially drugable candidate being studied is the PI3 kinase in aggressive disease. Other issues arising from clinical data are prognostic markers in primary tumours versus those present in metastatic disease.

ESGO 2013

Molecular profiling of primary compared to metastatic lesion in gynaecologic cancers

Prof Helga Birgitte Salvesen - University of Bergen, Norway
 

Helga, thanks for popping in because you’ve been looking, here at the meeting in Liverpool, at molecular profiling and endometrial cancer which is a cancer that we’ve heard there’s some progress in but perhaps not enough at the moment. So molecular profiling probably is really needed.

It seems like we really need to increase our knowledge regarding what are the true targets in endometrial cancer for improving the clinical trials.

What have you been doing?

We have done comprehensive profiling of paired, primary and now also metastatic, lesions under the assumption that if you are going to treat patients in the systemic setting  you will need to know more about what are the relevant and most prevalent targets in the metastatic lesions.

Now you’ve got some candidates, haven’t you, will you tell me what they are?

Well we have some candidates but the data are still quite immature so we need to explore more. From previous studies we have found that PI3 kinase signalling activation seems to be important in aggressive disease and we do find several of these PI3 kinase markers enriched and increased in the metastatic lesions. So they appear to be highly relevant targets in a systemic setting still.

And they’re potentially druggable?

They are potentially druggable and it needs to be explored in a clinical trial setting.

I know you’ve got mTOR as well as another one, the heat shock protein another one.

Yes. There are also indications that heat shock protein 90 inhibitors may be promising based on this molecular profiling and also PI3 kinase mTOR inhibitors.

What about the difference between markers that are present in primary tumours and those present in metastatic disease, is that a big issue?

It’s a big issue. Tumour heterogeneity is an enormous challenge for us. I think you can look at this in two different ways, you can think about what are the markers for developing aggressive disease, a prognostic marker. They will, of course, increase in the metastatic lesions because they are all aggressive cancers but if you turn it around the other way you can also focus on what are the markers you actually find in the metastatic lesions, regardless of their prognostic impact because you want to target them.

Exactly, and you can target them per se, you don’t necessarily have to worry about whether they were in a primary?

In a way that’s probably the case.

What are the clinical messages that could emerge from the sort of research you’re doing for ordinary doctors?

The clinical message is that this is increasingly complex unfortunately. We need to know more about what the status is in the metastatic lesions and we need to build our clinical trials around that knowledge.

So what would you say as a take home message to doctors who want to do their best for their patients with endometrial cancer right now? Have you made progress yet?

We make incremental progress by individualising the therapy, mainly by minimising side effects, maybe, at this point but there is a hope that we, through the clinical trials, can also improve the targeted therapeutics. That has to come.

Are you looking into molecular therapies for things like PI3 kinase, mTOR, heat shock protein? And there’s also hypomethylation, isn’t there, that could be targeted.

That’s also a possibility and there are indications that also the methylation status may change from primary to metastatic lesions but that’s also immature data that we need to explore further.

So in just a few seconds give me some optimism for the everyday hard working cancer doctor.

Comply with the trials, include patients in trials and we need to put more effort into achieving sequential biopsies and biopsies in the clinical trial context.

But you do think that endometrial cancer is a candidate where improvements can be made?

Definitely.

Helga, thanks for joining us.