Elaine Mardis - Cancer genetics

Kat - This month's I've been at the 10th annual National Cancer Research Institute, or NCRI Cancer Conference up in Liverpool, hearing from some of the brightest stars in the cancer research community. And, as might be expected, many of the talks touched on the faulty genes that drive cancer, and how we might target these to find new treatments.

The advent of DNA reading, or sequencing, technology has changed our understanding of cancer, particularly over recent years. Today we know that at its heart, cancer is a disease driven by genetic faults in cells, and that these can be inherited in some cases, but mostly arise throughout our lifetime.

One of the keynote speakers at the NCRI Conference was Dr Elaine Mardis, co-director of the Genome Institute at Washington University in Missouri. She's one of the thousands of researchers working on understanding these gene faults, and how they can be targeted with new 'smart' drugs designed to attack specific faulty genes and molecules in cancer cells. I asked her how things have changed in recent years, and where this brave new genetic world is taking us.

Elaine -   There's been an incredible transformation of cancer genetics and genomics over just the past short 5 years, and that's really been accelerated primarily by the advent of next generation sequencing.  So, these are new sequencing technologies, as of about 2007, that allow us to nowadays generate the data for an entire human genome - be that a cancer genome or a normal genome or both - overnight.  Of course, the analysis of that data is much longer than overnight.  But really, I think it has set the stage over the past 5 years for really teasing out the genetic underpinnings of cancer.  What is it about the cancer genome that that's much different than the normal genome in an individual?  And then expand that question by tens of thousands of individuals to really begin to understand across the board the similarities and differences in cancers.  This really now, I think from the discovery phase of the last 5 years or so, is setting the stage for what we call 'clinical translation' of the cancer genome.  So, how do we start as genomics folk to use what we've learned, to add to the diagnostic information that each doctor who's in the cancer cure sphere uses to help better treat each individual patient.

Kat -   Kind of lifting the bonnet on cancer now and seeing its workings, its genetic innards if you like.  What have some of these experiments told us about what is going on under the hood of cancer?

Elaine -   Right.  The basic discovery phase that we and others across the world have been in for these past five years has really revealed a lot, a lot that I think we didn't expect.  So, what are some examples?  So, I think one of the things that we traditionally have thought about cancer is that it has a lot of disease site specificity.  So, you'll see oncology specialists often divided into breast cancer, brain cancer, lung cancer.  And that's still the case, but what genetics and genomics has told us is that all those kinds of cancers and others share many of the same genetic alterations, whether it's in the cancer cells themselves or genetic alterations that are inherited or occur spontaneously.  So, that I think has been probably the biggest eye-opener, is that there's a lot more shared drivers of cancer development, if you will, at the level of the genome. 

I think the other surprise in all of this is that the more you ask, the more you find out.  And we've really as a result of that broader look, expanded our understanding of the functions of proteins that are mutated in cancer cells.  So, by studying the genes, we can extrapolate forward, if you will, to the impact of many of those mutations on the resulting protein.  That's really what plays out in the tumour cell and does all the work.  In that regard, some of the proteins that are now emerging that look like they are also causing cancer to develop are proteins that for example, add methylation or take methylation away from DNA.

Kat -   These are the marks that tells cells what to do with their genes.

Elaine -   Yeah.  They sort of tells which genes are on ,if you will, and are going to be turned into proteins and which ones are turned off.  Also, the proteins that organise the structure of DNA within cells are now being found to be frequently mutated.  We don't fully understand what that means in terms of the driving of cancer, but that's an area of active investigation.  I think this is a very exciting area that again was completely unanticipated by previous focused studies of the cancer genome.  So, all of these are kind of exciting to scientists as well as patients, as well as pharmaceutical companies.  Let's face it, because it really opens up a new area where we might be able to develop very effective and very targeted drugs against cancers.

Kat -   So, we found all these things that are faulty in cancer cells, maybe things we didn't expect, but obviously, what patients want to know is, how is this going to benefit me and if not now, then when?  So, how are we turning some of this genetic knowledge into actual treatments of patient benefits?

Elaine -   Right.  So, patients I think ultimately and even today are benefiting from the added information that genomics provides.  So, I talked earlier about how we were surprised that some genes that we thought were unique to certain cancer types are actually mutated in multiple cancer types, often unexpectedly.  What this means is that if that mutation is identified in your cancer, there may well be a targeted therapy that helps to address that cancer.  It could be added into the conventional chemotherapy regimen, you could qualify to be on a clinical trial and now clinical trials are considering a subset of patients that may be outside of these expected tumour types that can also get access to that drug if they have that mutation. 

So, I think this is, even right now today, a realised and realisable benefit for patients.  We don't want to suggest that genomics means that we need to leave all the conventional assays or investigations of cancers aside.  But just that it adds some additional information for the oncologist who is considering how best to treat the individual patient.  Ultimately, I suppose in the fullness of time, what we hope is that certainly, this added information will affect a larger number of patients who are alleviated from their tumour burden, as we learn better about how these therapies work, when they don't work, and so on and so forth.  So, it's early days, but there are some immediate benefits that are being seen by patients.

Kat - That was Elaine Mardis, from Washington University in Missouri.