European Multidisciplinary Conference in Thoracic Oncology (EMCTO) 2013

Advances and perspectives on biomarkers

Dr Nicola Normanno - Institute Fondazione Pascale, Naples, Italy

Nicola, you’re addressing from 2013 onwards the advances and perspectives for the future in all this thing about biomarkers for lung cancer because it seems that you can target an individualised therapy. You’ve got a lab specialising in this; you’ve been looking at some markers already, potentially you could look at a lot more. Tell me what you’ve been doing and what you’ve found.

Up to now we have only screened lung cancer patients for KRAS or EGFR mutations so for a very restricted number of mutations. Now we have available new tools that allow us to identify hundreds of mutations in dozens of genes and by doing that we can identify the specific targets for each individual patient and these, of course, will lead to improvements in personalised treatment for lung cancer patients.

Have you, in fact, identified hundreds of mutations already?

Yes, we have.

You have? And how many of them are concerned with cancer?

We have now a panel that is able to identify over 500 mutations in 22 different genes and we are now starting to use these in lung cancer patients. We can find a lot of patients that have indeed this druggable molecular alteration so that might be targets for therapeutic intervention.

How many of these are there, as compared with the ones for which you can’t do very much?

We don’t have yet a large number of cases that we have analysed but if we screen only for the EGFR mutation we can find the mutation in less than 10% of patients. Using these panels you can find druggable mutations in almost 30% of patients so we have a much higher number of patients that can get into clinical trials with the specific targets.

So you can get up from 10% to 30% in whom biological molecular therapies can actually do something about it, potentially.

Yes, let’s say potentially because of course this has to be validated in clinical trials. But at least we now start to find the patients that have these specific molecular alterations and we can put these in dedicated clinical trials and hopefully if they respond we will have new drugs in the clinic to treat these patients.

What are some of the rising stars in your lab?

The point is that many of these mutations are found in a very limited percentage of lung cancer patients, like 1 to 2 to 3%. So there is huge interest, of course, in BRAF, in KRAS and other mutations – RBQ, DBRQ, other genes that can be drivers of the growth of lung cancer.

But do you think that although individually these mutations may be responsible for just a small number of patients having lung cancer, they could potentially bring about remarkable remissions and cures for these patients?

Yes, if they will be proven that they are driver mutations, such as has been demonstrated for EGFR mutation or ALK rearrangement, we do expect to have significant effects of drugs targeting these targets. However, we know also that these tumours will become resistant so these tools are also important to assess the mechanism of resistance and maybe in the next future to have a second line of biological therapy for these patients.

Now, it sounds like a fascinating new world of potential cancer therapy but it is potential, much of it is potential, not proven at this point. What would you say to cancer doctors?

Well it is potential but we have preliminary findings for a number of biomarkers that they indeed might predict sensitivity to specific drugs. So now we have to wait for the randomised phase III clinical trials of course. But I think that in the next five years we will have a lot of new players in the field so a lot of new therapeutic opportunities for our patients.

And the take home message now for cancer doctors?

The take home message is that personalised medicine is moving really fast and in the next few years we will need to have a complete molecular profile of all patients if we want really to improve personalised medicine in lung cancer.

Nicola, thank you very much.

You’re welcome.