Investigating anti-carcinogenic compounds as an alternative to chemo
Dr Bernardo Bonnani - European Institute of Oncology, Milan, Italy
Where did chemoprevention come from?
Rather funnily it came up from the ideas of surgeons rather than oncologists. The very idea of chemoprevention arose from the simple thing that if we have carcinogens why can’t we have anti-carcinogens and we have them. It’s, of course, a matter of long study, long and very complicated studies, but the good news is that now we have good chemoprevention compounds. Some are already established.
Can you tell us about tamoxifen?
Tamoxifen came from another field of pharmacology; it was an oral contraceptive as the initial idea and then it was reverted in another field of research and then we came out with this wonderful anti-cancer drug. Then again, it was very much studied to see if it was a chemo-preventive compound and indeed it is.
Is it true that women who had tamoxifen showed less cancers in the other breast?
Exactly that and that is also the case of other more recent compounds like aromatase inhibitors. As a matter of fact, aromatase inhibitors are showing important chemo-preventive activity for the last few years, for example anastrozole and letrozole and exemestane.
How are you approaching chemoprevention in other cancers?
We have two other priorities, one is lung cancer the other one is colorectal cancer. Lung cancer we have been experimenting for quite a while with some compounds like budesonide, now we are completely ready to start another very important study with low dose aspirin for prevention of lung cancer. Again, in a model of study of lung nodules to be shrunk, possibly, by this compound, low dose aspirin. The other one is colorectal cancer; colorectal cancer may be prevented by other compounds, statins for example, metformin probably, possibly also vitamin D. This last compound is very much of interest, especially if you think we are now more aware of the role of the microbiota, the bacteria in our intestine which is very important and modulation by some compounds and some dietary compounds also may be of interest.
In colorectal cancer can aspirin be effective in chemoprevention?
It is absolutely chemo-preventative, absolutely, and it’s also chemo-preventive probably, even if not 100% certain, in those who are at very high risk for genetic predisposition also. So it’s very important to establish that definitely.
How do you identify effective biomarkers to work with in chemoprevention?
That’s very difficult and of course we have good biomarkers but as a matter of fact several candidate biomarkers coming from the lab pipelines are not yet used. So we are very much trying to work in a network with other centres, other centres in Europe for example and in the US, to study new promising biomarkers to be implemented in clinical trials.
What is the current situation with vitamin D as a preventative?
Vitamin D may be interpreted in two ways. One is that low levels of vitamin D may be a risk factor, so may be studied like a biomarker in fact. The other thing, the supplementation of vitamin D may be used as a chemo-preventive approach.
Do you have a trial planned with metformin?
We have applied for a grant at the moment in breast cancer chemo-prevention with metformin. The basis is that essentially we have to address not only the target subject, the target organ, but also the host itself. So especially if we know that metformin may act in several ways, so on the organ and on the host. It simply arose from observing the subjects treated with metformin who got less cancers and then the studies, the cancer studies, started. We are on the way showing that metformin decreases the risk of many cancers. This has to be proven completely, of course. For example, we have done a study recently in this very institute where we have proven that metformin is able to decrease cancer cell proliferation especially in the subgroup of those who have a high BMI.
You have a big meeting planned on chemoprevention?
In the framework of the EurocanPlatform programme we are in charge to plan a very important expert meeting in this institute. It will be an event addressed to experts, it will be essentially an expert meeting on chemoprevention and, to be more precise, on biomarker-based chemoprevention trials. The point is essentially that we have to discuss altogether among experts what is the current role of biomarkers and to address more than a question. For example, one big question may be why we have potentially a lot of biomarkers in the lab and just a few go to translational research and even fewer become applied in clinical research.
How will you improve on things going forward?
I think we will be in charge for discussing what are the best biomarkers at the moment, what are the best studies from phase 0 to phase I to phase IIa and b studies? Not discussing very much on phase III, of course something about that also. But essentially the very early trials just to be sure if we can impact on surrogate biomarkers before going to large cohort studies which is wiser.
Biomarkers as imaging is also important?
Absolutely, yes. It’s a larger concept of biomarkers, also molecular imaging for example, for sure, and also natural compounds may be biomarkers also.
What will you do with the results of this meeting?
Of course will write down a report, not a guideline, I would say, but an expert report of good use for the other experts and other people interested in that all around. The next step, I would say, is to start at least one or two more intelligent trials on biomarkers.
How many of the EurocanPlatform institutes do you plan to get involved?
As many as possible in the theoretical discussion and all that we can in the subsequent multicentre trials. The report will be disseminated through ecancer.
