Dr. Jo Bury, Managing Direct VIB (VIB: Flemish Institute for Biotechnology), Ghent, Belgium
There are so many different molecular mechanisms that all lead to the same type cancer, take breast cancer as a phenotype, but that have different ways of becoming cancer. And it’s only if we understand the molecular mechanisms that lead to that cancer that we will be able to find a target and treat it, to develop a diagnosis or a diagnostic to find the real reason behind it and to find a cure for it.
Scientists are just beginning to understand cancer
Much more needs to be done to fully understand cancer. We are working within VIB, there are about 50 teams working on cancer and they are all working on different mechanisms. For instance we know that p53 when it’s deficient it will lead to cancer. So about half of the cancers have been detected with a mutation in the p53 gene, but half of the cancers didn’t have any mutation in p53.
For the time being we are scratching the surface in terms of the drugs available on the market but within a foreseeable time there will be many mechanisms known, many targets identified for which drugs will be under development.
Once you have understood the molecular mechanism of a disease you basically have a clue or an avenue towards a diagnostics and a therapeutic. But in the future the two will go together: the diagnostic to identify the molecular mechanism for this patient together with the drug that is treating that molecular mechanism of this disease.
Finding biomarker to navigate in complex diseases is essential
Once you know the molecular mechanisms of a disease you can start looking for a diagnostic. On the other side we are convinced that may diseases have a kind of signature throughout the body where you can detect biomarkers that are part of that signature and which can provide us with early markers of something going on. I’m convinced that when you have a tumour that other proteins, biochemicals are produced by these cells that normally are not produced by these cells. But in complex diseases where multiple genes lead to that phenotype it might be more complex and it might lead to getting diagnostic profiles rather than a specific mutation.
But I’m convinced that basically the principles will be the same – it is understanding the mechanism of the disease and trying to manipulate it and to bring it back to where it should be - on the right path. So I think for complex diseases the approach will be more difficult, more complex but in principle will be the same.
Advances in technology – better understanding of disease mechanisms
The development of the technologies has been tremendously helpful over the last years. When I look back for instance to, let’s say 2007, 2008, it still took us like 20 million Euros to do the sequence of a full genome of a human being. Today, five years later you can get this for 1000 Euros. This is an amazing development of technologies. Five years ago it took us months to do it, today you can do it in one day.
As I see it - within twenty years from now cancer patients will survive on a rolling-over therapy with different therapeutic molecules coming one after the other and bringing them from one phase to the other surviving in a kind of ‘chronic mode’ as you do today with HIV.
The potential of sequencing in cancer is that one day we will be able to go to single cell sequencing. Once we go to single cell sequencing where you can identify at single cell level the mutations I think that the signal to noise will increase and you will indeed be able to detect what is a mutation and what is not a mutation.
The genomics, the proteomics today are providing us with the different parts of the puzzle. But we don’t know whether they are together, whether these parts form the complexes that you need to make them function in the cell. So what we need to see is not at the level of the genome but also at the level of the proteome: what proteins are there, whether they come together in the right complexes, whether they make the right complex structure that are doing the function, whether they are in the right place or not and if not what is wrong.
And so I would say the development of bio-imaging that is allowing us to see the complex forms and to see whether they are functional or dysfunctional this is a dream we have as scientists. We are working on that, the technology is called CLEM: Corrolative-Light-Electron-Microscopy and it will bring us to seeing how complexes of proteins are made and how they are functional or not. And then we will start understanding what’s wrong in the cell.