Fátima Al-Shahrour, from the CNIO in Madrid, came last week to the PRBB to give a talk entitled “Bioinformatics challenges for personalized medicine”. She explained what they do at her Translational Bioinformatics Unit in the Clinical Research Programme. And what they do is both exciting and promising.
They start with a biopsy of a tumour from a cancer patient who has relapsed after some initial treatment – they concentrate mostly in pancreatic cancer, but it would work with any, in principle. From this sample, they derive cell lines, but also – and they are quite unique in this – they generate a personalised xenograft. That is, they implant the human tumour in an immunocompromised mouse, creating an ‘avatar’ of the patient. After passing it from one mouse to another (they do about 60 mice per patient), they extract the tumour to analyse it by exome sequencing (and sometimes gene expression data, etc). They then have about 8 weeks to find, using bioinformatics, druggable targets that they then test on the avatar. Those drugs that work on the mouse are then given to the patient.
The advantages of this system are many and obvious: not only the in vivo model can be used to validate the hypothesis generated by the genetic analysis, but we basically have a personalised cancer model for a patient in which we can try as many drugs as we want. It can be cryopreserved, so we have unlimited access to the sample. And, since cancer is not a disease we can cure yet, but instead patients must keep checking out for possible relapses, metastasis, or resistances to treatment, keeping the mouse in parallel with the patient can help predicting how the patient will react to all these: whether he will develop resistance to the drug, which other mutations might appear, etc.
But there are several disadvantages, too. One is hinted in Fátima’s talk title: the bioinformatics analysis of the tumours to find which mutations are important (drivers) in the disease and which can have drugs that affect them is challenging, not the least because an individual cancer genome can have hundreds to thousands of mutations.
Perhaps the biggest barrier is that, at the moment, making these avatars is inefficient, very expensive and slow. And since the patients who are benefit from this technology are already in a very bad clinical condition, many of them don’t get to live enough to enjoy those benefits. But there are some successful cases, and Fátima mentioned a couple. In one case, a man with pancreatic cancer who was treated with mitomycin after all the tests in his avatar, survived more than 5 years, when he had been given 1 year at the most.
So there is hope in the field of personalised medicine, despite the fact that this is still not standard, and won’t probably be for the near future. And, as someone in the audience mentioned, in an ideal future, we might even have personalised prevention, according to our genetic makeup. Wouldn’t that be great?
A report by Maruxa Martinez, Scientific Editor at the PRBB