6th International Kidney Cancer Association Symposium, 6—7 May, 2011, Warsaw

Biomarkers to individualise kidney cancer treatment

Professor Giampaolo Tortora – University of Verona, Italy

Now there is a lot new in renal cancer because in these past five or six years many drugs have entered finally the arena of our therapeutic armamentarium that we have available, so we started from a disease for which we had basically nothing, because it is radio-resistant and chemo-resistant and we had only the chance to use immunotherapy as our only therapeutic option, to a disease for which now we have six drugs available and more are getting into the arena. So there have been a lot of changes for treatment and, fortunately for patients, impacting on survival and quality of life of these patients.

Are all of these drugs active?

All these drugs are active. There are many; they belong to a few different classes, and a problem which paradoxically we are facing today is to find out which drug to use first and which is the best sequence of drugs to be used. Because we know that if we use the drugs in an appropriate way we can give a maximum benefit to patients. So the problem is how do we figure out which is the best drug to use first and which is the best sequence, and how to tailor this information on the patient in order to get the maximum benefit from treatment. In these past few years we also learned that there are specific molecular lesions which are characterising the different histotypes of renal cancer. We know there are different histotypes, the most frequent one is a renal cancer of clear cells, so-called clear cell, which is the most frequent but there are other types, less frequent, like the papillary type 1 and 2, the chromoform and so on. Today we know that each single histotype has specific molecular lesions and specific features. What we are trying to do is to correlate the molecular lesions and some particular features occurring within these different histotypes with sensitivity to drugs.

This is a very important aspect because our final goal is to give the right drug to the right patient at the right time. In order to do so we have to find out what we call biomarkers, even because most of these patients first benefit from treatment and then they develop resistance which is a typical phenomenon that unfortunately occurs in cancer which adapts to the different pressures that we pose with treatment. So the tumour tries to escape by using a particular type of strategy and we have to follow these escape pathways and chase the tumour. So biomarkers can help us to figure out which patient can benefit most from each single treatment, and also will allow to overcome resistance or prevent the onset of resistance. And this is the reason why now the great majority of studies are looking for biomarkers. You can measure the biomarkers on the tissue, so it is like the work the pathologist does, or you can measure the biomarkers in the plasma or, possibly in the near future, also in the urine or other biologic fluids.

Today a lot of work is done on the plasma because you can withdraw blood and follow the disease, follow the treatment, and find what is new. And several new findings are helping to discriminate which could be the patient benefiting most from each single drug, but we are at the beginning really and in this phase we have important information but we are still in the phase in which we are trying to understand which are the most reliable biomarkers, because there are many and only a few of them will be very helpful. So there are some technical problems that are now on the way to being overcome and resolved, and other problems which are more related to the class of drugs that we use. But this is a very promising area and the final goal is what we call the tailored therapy: to give the right therapy to the patient based on the single specific features that the tumour of that patient has rather than being very generic, giving every drug to everyone just to get very little result from each one.

Are there clinical trials for these biomarkers yet?

The clinical studies now are not based on biomarkers and this is actually a major limitation that we have and probably this is affecting the results of our studies because so far we do not have yet reliable biomarkers that we can use to discriminate single patient populations. So unfortunately, to date, we are giving drugs to all patients without knowing who is going to respond and who is not. So we are trying to find out now why some respond and some do not.

There are many, many clinical trials ongoing right now exploring different drugs, different sequences, and an important feature of all these trials is that the large collection of samples, including plasma samples, is a critical part of the trial. This is because we have to understand and learn why some patients will respond and some not. Of course, once we have this information, based on the results, we will try to use this information to design the next trials in which patients receive the treatment based on specific biomarkers. So far we can’t do that so we just measure biomarkers, see the results of the trial and match the biomarkers with the results and then try to learn.