How will genomics be applied to patient therapy in future?

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Published: 30 Apr 2015
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Dr Jean Claude Zenklusen - Director, The Cancer Genome Atlas

Dr Zenklusen talks to ecancertv at AACR 2015 about how genomics can be applied to therapies and what difference this will make to patient treatments. 

He also explains what the issues are with targeted therapies, in relation to his knowledge of genomes.

We are some years away for genomics to be applied to therapy and to make a difference in the way patients get treated.

But it is a process that is happening and, in fact, in some tumour types already is happening in the research institutions.

It’s not something that is happening at the community cancer hospitals but it will get there.

Can you tell me in terms of day-to-day medical practice what has happened so far?

One of the big things that has happened is that we are identifying subtypes of the tumours based on the molecular characteristics and not on the organ where they come from or what they look like under the microscope.

That has made a change.

One example would be low grade gliomas, they were always supposed to be tumours that you had time to intervene because it takes longer for the tumour to kill.

But we always knew that some people with low grade gliomas did react very badly to the cancer and now we know why.

These tumours look exactly like GBMs, the glioblastoma multiformes, which kill most people with brain cancers.

So being able to identify these cancers very early on makes a lot of difference for the patients in the way they get treated.

And that means you can individualise therapy, does it?


We can; we have classified sets that we can define from the 33 tumour types that we have analysed we can define subtypes.

We know what the molecular markers are and what makes them tick and so we now can very specifically target to those molecular changes and make a difference in the way the patients get treated.

In the common tumours, though, are there any genomic features which are floating to the top that could give you an edge and actually help millions of people?


For some tumour types like lung we need to delve deeper because they are very complex, they have high levels of mutations so we have just scratched the surface.

But some other types like breast we have enough information to make a difference.

We have one subtype of breast cancer that really looks very similar to ovarian cancers and these ovarian cancers look very similar to these particular subtypes of breast cancer.

As you know, ovarian and breast are epithelial but they are very different.

What this is telling us is that the changes have been so dramatic that these tumours are behaving as a totally different entity from the cell of origin.

That makes a difference also because you have to go more aggressively to those.

We live in an era of targeted cancer medicine and yet that target is moving. Can you throw any light on that whole process with the genome knowledge that’s coming out now?

The problem we have with targeted therapies is that eventually the patient will become resistant to the therapy.

The reason the patient becomes resistant to the therapy is that with targeted therapies you have one single Achilles’ heel that you are going after.

If all the cells in the cancers don’t have that Achilles’ heel you are going to end up selecting for a clone that will start growing again and is resistant to the therapy and that is what we are seeing.

So what will happen and needs to happen is an investigation on how we can put together a multiphasic approach to therapy.

Basically we still need to use targeted agents but we need to use them in combinations that make sense according to what the molecular profile of the patient is.

In fact, I see in the future that we are not going to classify the tumours as breast tumour luminal or oligodendrocytoma stage 2, we are going to say, ‘Well, you have a tumour that has mutations a, b, c, d and e and so, since you have these mutations, we need to give you therapeutic agent A, B, C, D and E and maybe toss some F in there to make sure that it gets better.’

So we’re not there but we’re approaching at a really, really fast pace.

So finally what do you advise cancer doctors to be doing about this whole business right now?

I think the best advice I can give any cancer doctor, and any patient too, is that these combinations of mutations are very complicated.

Really no-one that has gone through medical school that is alive today has had an education on this.

But we do have a group of professionals that know how to deal with this and those are the genetic counsellors.

So my advice will be if you get these patients and if you get this analysis and these diagnostics done on these patients, get together with a genetic counsellor, they are going to be very informative and they are going to help you a lot in figuring out what you can do for the betterment of the treatment of your patient.