IGCS 2012

Defining and advancing individualised medicine

Professor Anil Sood – MD Anderson Cancer Centre, Houston, USA



Dr Anil Sood, it’s great to have you here in Vancouver all the way from Texas, the MD Anderson. I’m going to ask you about the symposium that you took part in; it was about individualised medicine, what is individualised medicine. This is a question that’s being asked all the time, isn’t it, a difficult one. What were you trying to do in that talk?

Thank you for having me. For this particular symposium we invited world’s experts on addressing what exactly does individualised medicine mean and how do we move this forward in a practical way over the next several years. So the way we think about individualised medicine is that rather than treating all patients in a generic same manner, really think about how to harness the power of the new genomic medicine and other patient-specific factors and design treatments, prevention approaches, that are uniquely tailored for a given patient.

Let’s get down to specifics because you were addressing gynaecological oncology, of course. What sorts of leads are there here genomically?

Let me give you one example that has been really very much of a success over the last several years. We now know that women who have a BRCA1 or 2 mutation tend to respond much better to something called PARP inhibitors. These are relatively new inhibitors but women who have cancers with BRCA1 or 2 mutation just respond tremendously well to these kind of inhibitors. That’s an example where you can tailor the therapy to a given genetic change in that given individual whereas these inhibitors tend not to be as effective in others who don’t have these kinds of changes.

Of course at the cellular level and in the laboratory you can find these tempting, these tantalisingly hopeful ideas, but what about in real practice in the real world?

Well this is in the real world now because there have been a series of clinical trials that have basically demonstrated this. This came out of laboratories of investigators around the world where the key finding was that certain drugs like platinum or PARP inhibitors just worked so well in individuals with the BRCA 1 or 2 mutations or at a broader level, something called homologous recombination defect. So now in clinical practice over the last few years that’s certainly borne out for ovarian cancer.

And what sorts of hopes came out of the symposium, specific ones?

Many things. That across different gynaecologic cancers, in ovarian cancer there have been a number of genetic defects that have been identified that hold promise for developing new therapies that are at a very, very individual level. In endometrial cancer we know that those women who have cancers with hormonal receptors can have a good response to anti-hormonal agents. In addition there have been other pathway abnormalities identified and now there are a series of clinical trials on-going. For cervical cancer it’s a bit earlier but there are a number of changes that are certainly also attractive.

OK, looking at these pathways, if you were to pick out one that looked really promising at the moment, what’s that?

Again there are a number. The two big successes in ovarian cancer so far have been with PARP inhibitors and with tumour microenvironment targeted drugs. We talked a lot about that yesterday, so a pathway related to vascular endothelial growth factor that promotes a blood supply to the cancer in ovarian cancer and in some of the other cancers, even individually targeted, has shown promise. To us these form important platforms upon which to build additional therapies.

So we’re back to angiogenesis being a big factor?

Absolutely.

Talking about ovarian cancer, you’ve got the Moon Shot now, a new initiative. Could you tell me all about that please?

Absolutely. At MD Anderson something called a Moon Shot initiative has recently been launched and the analogy is that as President Kennedy in the 1960s gave a charge to reach the moon, he didn’t say, ‘You should study how to get to the moon,’ but there was a very specific charge. So our President has charged individuals around the institution for specific cancers to come up with a blueprint to substantially improve survival over the next ten years, ultimately leading up to a cure. This is not a narrow focussed approach; this is a very, very broad approach that’s comprehensive in the sense that for prevention, for early detection, for therapy, even for survivorship and minimising the effects of therapy and, of course, understanding new biology, all of that will be covered under the Moon Shot programme but with a very specific goal that you have to make huge increases or improvements in survival as a result of what’s done. So it’s a very comprehensive transformational programme in terms of how we think about cancer management.

To what extent do you think this is attention to detail is going to reap these benefits or are we looking here for big advances?

We are looking for huge advances, attention to detail is fundamentally critical. So for every project that becomes a part of the Moon Shot, there will be go/no-go decisions along the way, such that those things that don’t look promising will be stopped at an earlier time point and those that indeed look promising will continue to get invested in and get ultimately engaged into the community for patients. And again it’s even broader than that, the goal is even to influence policy if that’s what needs to be done.

So you actually do need to make some tough decisions. There may be people really enthusiastic about a particular pathway but it might not be productive.

That’s absolutely right.

That’s difficult, isn’t it?

Of course it’s difficult but I think in the setting where you have a very specific charge and a goal in mind, you have to make difficult decisions.

I need to throw one thing in to you here, platelets. I think there’s news about platelets at the moment, isn’t there?

Yes, absolutely. Over the last year we published a study related to why do platelets go up in cancer patients? The finding that blood clots can develop in cancer patients has been known for over a hundred years but never has there been any specific reason elucidated for this. So what we figured out is that about a third of ovarian cancer patients have very high platelets, those who have high platelets tend to live for a shorter time period, they don’t respond to therapy as well and the reason they have high platelets is that the tumours start producing certain growth factors that stimulate the liver to production of something called thrombopoietin which results in production of megakaryocytes and very high levels of platelets. If you disrupt this pathway then you can block the platelets from going up. So it’s a very, very important finding because it’s resolved something we’ve known for a long time.

Yes, but do you have real hope of disrupting that pathway and doing something about it?

Absolutely. We collaborated with a group in the UK where they used an antibody targeted against interleukin 6, which is one of the main drivers of high platelets. If you disrupt interleukin 6 within three weeks the platelet counts came down to more normal levels in human patients. So we have, at this point, evidence even clinically that you can make a difference by disrupting this kind of pathway.

OK, now you’re a broad church at MD Anderson and you’ve addressed the broad issues – individualised therapy, the Moon Shot. Would you pull one or two things out of this that you’d like people to remember from this meeting here in Vancouver?

This meeting is at a pivotal point in cancer research and treatment. It comes at a point where a lot of the technologies are fundamentally converging that provide us with a very important toolbox for making massive discoveries and really having an impactful outcome as a result. So this meeting culminates a lot of that kind of knowledge together in a way that couldn’t have been done in the past.

So, words of encouragement for cancer clinicians and scientists?

Absolutely, yes.

It’s great to have you with us, Anil, and I look forward to hearing more in the near future.

Thank you very much.