Like many other great discoveries made in science, chance played an important role in the last article published in Cancer Cell by a team of researchers from the Signalling and Cell Cycle Laboratory at IRB Barcelona. "I think we were lucky, but we also knew how to take advantage of our luck," says the biochemist Begoña Cánovas, co-first author of the article, together with Ana Igea.
This success story started back in 2011 when Angel R. Nebreda’s Signalling and Cell Cycle Laboratory moved from CNIO (Madrid) to IRB Barcelona. Among many other things (from big machines to tiny gene copies), they brought with them some mice that were about to be discarded. They had been generated to develop tumours under specific conditions and they weren’t turning out as expected.
But rather than discarding these animals, Begoña Cánovas (born in Galicia, Spain, 1986) and Ana Igea (born in Barcelona, Spain, 1981), under Nebreda’s guidance, decided to find out what was going on in these animals. Six years later and after a great deal of perseverance, they have discovered that p38 repairs 'in extremis' the DNA of cancer cells, thereby preventing them from dying from the accumulation of damage. In addition, using mice, they have demonstrated that the combination of standard chemotherapy drugs with p38 protein inhibitors (which have already been tested and are available on the market) enhances the effect of the therapy, causing the tumours to shrink. This discovery may also lead to a diagnostic tool to identify those patients that would respond favourably to combination drug treatment.
Ana, IRB Barcelona Alumni and Research Associate at the University of Vigo, and Begoña, Postdoctoral Fellow with the Signalling and Cell Cycle Lab, have spent many hours working closely together—and the excellent relationship between them stands out.
Begoña Canovas: I am a Biochemist and I hold a Master’s in Bioengineering. After a short stay in the Massachusetts General Hospital (Boston), I came to IRB Barcelona to do my PhD. This project has been the cornerstone of my doctorate.
Ana Igea: In my case, after completing my PhD at CRG, I wasn’t sure whether I wanted to pursue a career in research, so I first joined IRB Barcelona as a Lab Manager to help set up the lab here in Barcelona. But I was intrigued about what was going on with the mice and I ended up in active research again. This project has kind of reconciled me with science.
BC: No, not at all! At first, we only wanted to see the effects of eliminating p38 in the breast cancer cells of these mice. We observed that they grew less, that they had DNA damage, and that they showed defects in the division process. We realised that many chemotherapies used to treat cancer are based on the same mechanism of action.
AI: Since we were backed by an ERC grant, we started to address whether p38 inhibitors could boost chemotherapeutic treatments, and that is precisely what we found. The enhancing effect was evident in cells in vitro! We then studied this in mice and confirmed our findings.
BC: Actually, this first brought about some months of hard work addressing the issues raised by the reviewers, and the jitters. The first time we submitted the article for publication, the referees drew our attention to a “weak point” of the paper, and this was something that we were able to sort out. But in the second round, one of the referees asked for more and more experiments and I was at my wit’s end.
AI: It has certainly been a long and hard review process, but with a happy ending.
AI: No, we weren’t, and we were amazed. Good publications sometimes don’t have that impact. But I suppose that because the topic was cancer, our findings had been tested in mice, and the drugs involved are already on the market, our study is closer to having an impact on society. Also, the Communications team at IRB Barcelona did a great job.
BC: Yes, I totally agree. We knew that it was a good study and we were obviously pleased about getting it published in a good journal, but getting your picture in the newspaper is another thing altogether...!
AI: About a year ago, I took up a Research Associate position in the Immunology Group at the University of Vigo. For me this publication is recognition of my work at IRB Barcelona and an endorsement of my capacity as a researcher.
BC: The first thing this article meant for me was me giving myself an ice skating course (she laughs), and I have already passed two levels! Apart from this, I am in the process of completing a few pending projects, and I have to sit down and think about the next stages of my career. I still don’t have a clear idea about where I am heading, but, wherever it is, this study will open doors for me.