FOCUS | turning points FOCUS | turning points Standing on the shoulders of giants Samra Turajlic is a consultant medical oncologist at the Royal Marsden National Health Service Foundation Trust and a clinician–scientist at the Francis Crick Institute. Samra Turajlic

uring my medical training Martin and James were working with in 2007, I met a patient named Charlie Swanton, also a clinician–scientist DMichael. He was 27 years old and at the Francis Crick Institute, on newly diagnosed with advanced . evolution. Joining his lab would be another Michael received chemotherapy, the only turning point in my journey. We not only standard treatment available at that time. treated patients with melanoma, but also But his melanoma continued to spread to those who had renal cancer. The clinical his liver and brain, and he died just three course of renal cancer was bewilderingly months after our first meeting. varied, and I wondered whether this Michael’s story was not unusual. On was underpinned by cancer evolution. average, patients diagnosed with metastatic Answering this question involved dozens melanoma survived for six to nine months, of colleagues (clinical and academic) and chemotherapy was largely futile for and our patients, whose commitment this disease. Melanoma was often referred kept the project going through taxing to as an ‘orphan cancer’ because of the lack times including collecting and analyzing of therapeutic progress for decades. This thousands of cancer samples. fueled my desire for a more fundamental As I was writing this piece, Martin understanding of the problem. I had Gore died unexpectedly. For over ten not taken to laboratory research as an years, Martin provided me with infinite undergraduate. But at the time, new findings kindness and wisdom, unconditional from basic research suggested that there may Credit: The Royal Marsden. support and exceptional humor. He leaves have been unexplored options for treatment a void that is impossible to fill, but I also of melanoma, so I wondered if I could help realize how fortunate and privileged I find answers by going back to the lab. In the lab, we tested BRAF inhibitors using am to have worked so closely with him. Preclinical evidence was emerging in vitro and in vivo models developed from I would certainly not have become a that inhibition of BRAF, a protein that patients’ tumors. Simultaneously, these clinician–scientist if it wasn’t for Martin’s usually stimulates growth, could be an results were compared with responses championing. Martin taught me that clinical effective treatment for melanoma. In 2002, of patients receiving BRAF inhibitors in medicine and science were not so far apart, scientists, including Richard Marais at the clinical trials led by Martin and James. as many claimed. He argued that oncologists Institute of Cancer Research, discovered The treatment was working, sometimes owed it to their patients to create research that in the BRAF gene drive spectacularly, which was revolutionary for opportunities in the course of caring for the growth of melanoma tumors. Richard, an ‘orphan cancer.’ them. As of today, the average survival along with Royal Marsden Hospital’s I returned to oncology training after of patients with metastatic melanoma is leading oncologists Martin Gore and James completing my PhD in 2013. There were around four years, up from less than a year Larkin, was investigating drugs that targeted a lot of myths surrounding clinician– about a decade ago. This progress came with mutated BRAF. These scientists, including that we couldn’t do about through a coordinated dedication of three were also looking for a clinical PhD authentic science or engage in meaningful scientists, clinicians and patients, and this candidate who would not only train in basic clinical practice. Martin Gore was an made Martin proud. I hope that through science but also integrate the basic work essential mentor to me and was instrumental my involvement in clinical and basic science with clinical research. The opportunity to in boosting my career as a clinician– I can honor his legacy. ❐ work with them was a major turning point scientist. Martin argued that I use my in my career and life. knowledge of and cancer Samra Turajlic1,2 The change didn’t come easily. Being genomics to tackle emerging clinical issues, 1Te Renal and Skin Units, Royal Marsden NHS used to the fast pace of a clinic, I frequently such as resistance to therapies and the Foundation Trust, London, UK. 2Te Cancer attempted to run too many experiments at potential for harnessing the immune system Evolution and Genome Instability Laboratory, once, much to the amusement of my lab to treat cancer. In our patients with BRAF- Te Francis Crick Institute, London, UK. colleagues. The interface between the clinic mutant melanoma, resistance was inevitable, e-mail: [email protected] and lab was immensely powerful, however. which was painful to witness. It became We were part of one of the finest (in my clear that resistance was a result of cancer’s Published online: 6 March 2019 opinion) examples of research translation. ability to evolve and adapt. https://doi.org/10.1038/s41591-019-0389-3

Nature Medicine | VOL 25 | MARCH 2019 | 356–357 | www..com/naturemedicine 357