Dr. Mauro Ferrari of the Houston Methodist Research Institute.

The Promise of Precision Medicine

A Conversation with Dr. Mauro Ferrari of Houston Methodist Research Institute

Ever since the human genome was successfully mapped a little over a decade ago, medicine has never been the same. We’ve learned more about how to prevent and target disease, and also how each individual can respond to disease and treatment differently. Enter precision medicine: a much more personalized, targeted form of medicine that will have a great impact on biomedical research and care.

To better understand precision medicine’s promise and potential, we recently spoke with Dr. Mauro Ferrari, President and CEO of the Houston Methodist Research Institute, where precision medicine is a fundamental strategic research area. Ferrari spoke at the TAMEST Texas Research Summit on Nov. 13, a one-of-a-kind event bringing together Texas’ top scientists and federal research agencies to highlight the outstanding research and innovation taking place in Texas. The objective of the summit was to better understand federal research priorities so that Texas institutions are more competitive in seeking federal funding.

How would you explain what ‘Precision Medicine’ is?

“It’s a pretty obvious notion, if you think about it. It’s the notion that for any individual patient, you will be given the right treatment at the right time.

Today, with science, we are able to differentiate different situations that before we couldn’t tell apart. For instance, with breast cancer — there was a time not too long ago when all breast cancers were considered to be the same disease. Now it turns out there’s many different sub-groups of that, many different situations that require intervention with entirely different drugs.

Dr. Mauro Ferrari in the lab.

So the question is picking the right drug for every patient. Because with cancer, for instance, as the disease progresses, it changes. The cancer today may be vulnerable to certain medicines, but in the same patient, the disease tomorrow, or next week, may develop resistance to certain medicines, and will only be treatable with a different type of drug regimen. So it isn’t obvious how you pick the right treatment, even though the disease may be nominally the same. This is what precision medicine is about.”

How could advances in precision medicine change the experience of patients? Could certain types of care become less intensive or invasive?

“In cancer, it’s always about balancing the beneficial effects of treating the cancer with the potential adverse side effects which accompany pretty much any medical intervention, especially cancer chemotherapy. So by selecting the right drugs for the right patient at the right time, you can do both. You can increase the therapeutic efficacy and you can reduce the amount of unnecessary adverse side effects.

For instance, there’s a special type of breast cancer mutation called HER2 positive, it’s about 16–20% of all breast cancers. And for these cancer patients only, there’s a great drug called herceptin, one of the first molecularly-targeted drugs that’s very effective against the disease. Well the same drug doesn’t do anything for the 84 percent of breast cancers that don’t have the mutation. So for the patient, it really means you either have an efficacious therapeutic strategy or you don’t. It can mean life or death.

If you give patients a drug that’s not molecularly tailored for the patient’s disease, all you get is side effects. So you go through the suffering of therapy, you burn out, if you will, and in exchange for that you get nothing. Instead, with precision medicine, you could have had a different treatment, perhaps an experimental one, with beneficial effects. So the importance of being very precise with precision medicine in many cases is a difference between life and death. We’re never going to be able to cure effectively the types cancers we need to cure now if we don’t make progress in precision medicine. It could not be more important than that.”

What are some of the major accomplishments or results from Texas research institutions in the field of precision medicine?

“Typically, when people speak about precision medicine, again in the concept of cancer, they’re thinking about specific gene alterations or gene mutations that accompany certain forms of cancer, like HER2. If you can pick a drug that will target cells that have that gene mutation, then you’ve accomplished precision medicine. A great early example of this strategy comes from MD Anderson Cancer Center where Dr. John Mendelsohn was a great pioneer in this. He was instrumental in bringing the groundbreaking drug Erbitux to the clinic.

Dr. Ferrari speaks at the Texas Research Summit.

Historically, precision medicine, which has really only been around as a term for about ten years, has been seen as finding the gene that has mutated and targeting it. Now it turns out there are other components, other parts of the story.

A different part of the story is the way drugs penetrate through the body and reach the right location where the cancer is different in different patients. It’s not only enough to get cancer drugs that are specific to the cancer type, but we also need to have a way to vector the drug in a way that is specific to the patient. And here is where nanotechnology comes in. It’s about personalizing the delivery system — that is the type of work that we specialize in at Houston Methodist.

A few other examples of precision medicine: The world powerhouse of medical genetics and genomics for many years has been the Baylor College of Medicine under the leadership of Tom Caskey in the department of genetics there.

Are their areas of research where Texas institutions are having a distinct impact?

One aspect that’s more contemporary is the work that’s done in understanding how to transport medication, that’s a discipline which is called Transport onco-physics, the physics of transport of mass, cells, drugs, molecules and cancer, that’s an entirely new discipline.

One young extraordinary scientist in the field is Eugene Koay at MD Anderson, who has demonstrated that you can use essentially physics and image analysis to predict which therapy is going to be helpful for which patient, not on the basis of gene profiling, but on the basis of the physics of transport, as you can see from imaging the patient — it’s an entirely new approach.”

Aside from more research and funding, what else will be required in order for precision medicine to become more prevalent and effective?

“First of all, the more people that are aware of precision medicine, the better it is. We need to get the word out on what it is.

The other has to do with how we do the research. Precision medicine is no longer the domain of the cancer geneticist alone, it takes a team of people working together — geneticists, molecular biologists, physicists, engineers, chemists, and mathematicians. It’s a team effort now, so we need to find ways to evolve the silos of science so that they’ll merge and come up with solutions that are truly multi-disciplinary. No individual discipline by itself can figure it out.

Another point has to do with pharmaceuticals, the way in which therapies are approved and brought to the market. There’s a philosophy of the pharmaceutical industry — developing drugs that can apply to a very large group of patients, for obvious financial reasons. Well now if you look deeper and deeper and figure out no two cancers are alike, all of a sudden you have a problem that the best drug for me may not be useful for other people, so how do you bring that to a clinical trial? It’s counter to the way we’ve been doing pharmaceutical development.

So we need to identify a new way for market forces to be satisfied, and of key importance to that is how we do trials. Right now it’s required to do clinical trials on a very large group of patients whose diseases are nominally identical. Well, it turns out that may be a strategy that we need to modify somehow, and I’m not sure how. The right drug might only be right for three people, but there’s no way to do a clinical trial on such a small group. So we need to rethink how we do clinical trials. I don’t know what the answer is, I only know there’s a need to find one.”

To collect the massive amount of personal information needed for precision care, how do you address concerns about privacy?

“This is one glaring example of the trade offs we’re faced with in this age of big data. In my opinion, the best way to look at the balance of benefits and risks of privacy and precision medicine is to not leave it to the scientists or the IT expert. This has to be a societal decision. How much of our right to privacy is it fair to give up in order to live more safely? We as scientists have to listen to society to come up with the right solution.”

Read more about the TAMEST Texas Research Summit.

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