Molecular biomarkers and acquired resistance to new target agents

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Published: 31 Jan 2011
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Dr Luca Toschi - Istituto Clinico Humanitas, Milan, Italy

Dr Luca Toschi speaks about molecular biomarkers and acquired resistance to new target agents. A number of speakers at ESMO 2010 have stressed the important of collecting tissue samples before treatment in order to identify any potential biomarkers and this is likely to become more important as the cost of cancer treatments increases. Dr Toschi discusses the steps that must be taken to improve the link between the laboratory and the clinic and outlines his work developing cost effective techniques for clinicians to identify which treatment is most likely to be effective for each individual patient.

35th ESMO Congress, 8–12 October 2010, Milan

Interview with Dr Luca Toschi (Istituto Clinico Humanitas, Milan, Italy)

Molecular biomarkers and acquired resistance to new target agents

Can you tell us a bit more about the implication of your research for the clinic and also about your research before coming here to Milan, because I know that you were working at the Dana-Farber Institute in Boston.

Yes, I spent a couple of years in Boston doing mostly pre-clinical research and trying to identify molecular biomarkers involved in acquired resistance to new targeted agents. I’m trying to translate our laboratory findings in clinical research right now. So we have a strong focus on biomarkers in terms both of identifying prognostic and predictive factors to standard therapies, either cytotoxic agents or new targeted agents. Clearly what is also emerging, very importantly, here at ESMO is several speakers say that tissue is the issue, so really to collect tissue from our patients prior to treatment and try to perform all the molecular analysis which we deem to be essential to identify those potential biomarkers.

In fact most of the new agents that have been introduced in clinical practice have huge costs so we have to imagine that in the long run these costs will become unbearable from the perspective of the national health systems. Considering particularly these agents have benefit in about 30 – 40% of the patients so we need to find tools to better select our patients and to deliver them active agents.

That’s very interesting. Can I ask you two things – one, can you name a few of these biomarkers that you’re working on? And the second one is a point related to cost and how does economics impact because it’s a very important issue and not many people talk about it, so maybe you can tell us a bit more about that?

Yes, cost definitely presents a huge issue, not only for new targeted agents but new cytotoxic agents, a reflection of the major efforts that have been carried out by companies to develop a new cytotoxic. In fact most of the drugs were initially developed only in unselected populations but right now all the companies have to sustain lots of costs because of all the pre-clinical and clinical drug development, trying to identify biomarkers by themselves. So particularly I have been focussing on mechanisms for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors and also sensitivity. We have been studying EGFR mutations which are emerging in the last few years as the most reliable predictor of benefit for patients who are treated with EGFR TKIs. We are also trying to focus right now in my institution on molecular predictors to specific cytotoxic agents.

So how is this going to impact on the clinical decision-making in terms of therapy for the single patient?

Clearly we have to identify cost-effective tools which we can perform almost in every lab to be able to get a quick result and to tell your patient which is the best therapy which you can use. Right now, for example, for EGFR mutations genotyping is not feasible in all hospitals, in all institutions, so you lose about two to three weeks to prepare your samples from the pathology department and to send them to a central lab for analysis. So we really need to be very careful and try to identify quick and cost-effective tools to identify our potential biomarkers for patient selection.

So clearly we want to tell a patient there is an 80% chance that this drug is working in your case and not just the 10 – 30 or 40% which is what is happening right now.

So stratification?

Right, biological and clinical, but mostly biological patient selection.

You mentioned one of the problems was translation - the fact that not all hospitals or research institutions have laboratories that can perform the tests and you have to send them somewhere else? So since you are co-ordinating the translational research project, can you give us some suggestions or tell us what you think are the steps that need to be done to have a better collaboration between the laboratory and the clinic, so from the bench to the bedside?

Yes, I think there are three major ingredients. You need to have patients, you need to have funds and you need to have the expertise. So I would say these are the three main features in order to develop a well-equipped lab with all the expertise around the experiments. You also want to be sure that you have reliable results, so there will also be important issues with EU certification for all the labs that will be performing this diagnostic test.

And does your institution have these three ingredients? Or do you think that a multi-centre effort is better suited to do it?

No, right now we do have all these features and particularly the pathology department is in charge of all this analysis but we are developing our translational research lab just for the oncology department which, in perspective, will be very useful also for the patients.

Not only for lung cancer but also for others?

Right, also for other solid and haematological malignancies.

So a last question – are you planning to collaborate with other institutions in Milan or what are your next projects?

Yes, we have a bunch of projects which are involving other institutions, not really in Milan at the moment, but in Italy and we still have some collaborations with Boston and Denver, Colorado also. But we are definitely doing some networking.

Thank you.