Prof Sebastian Nijman develops new approaches to study signalling networks in cancer cells and to uncover specific weaknesses, particularly in breast and lung cancer. This knowledge can be used to develop more effective targeted drugs and to better guide treatment decisions.
In the context of cancer, genetic diversity means that we respond differently to various treatments. Pharmacogenomics sits at the intersection between genetics and drugs. Better understanding of the genetic landscape of cancer and the recent increase of targeted drugs allow us to better match patients with the best treatments, improving care.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: What is pharmacogenomics?
Sebastian Nijman: Pharmacogenomics deals with understanding how genetics and pharmaceuticals interact with one another. If you go to the doctor, he or she will typically take into consideration your symptoms and then try to diagnose a particular disease and match the therapy that goes with that. Taking your genetics into consideration is rarely done, even though we know that this plays an important role. This is particularly true for cancer where we know that there is huge genetic diversity and a differential response from patient to patient, so that is what pharmacogenomics tries to address.
Q: How does it impact on cancer treatment?
SN: Pharmacogenomics impacts on cancer treatment because, when successful, we are better able to match the patient with treatment and thereby improve the care of the patient.
Q: How does pharmacogenomics help develop new therapeutic strategies?
SN: It doesn’t directly, with pharmacogenomics research we don’t necessarily try to discover new targets, although in my lab we do that as well. By studying drug action and learning about precisely how they work in the setting of genetic changes, we can often learn something about the drug and thereby as a by-product discover new drug targets. For instance, in a recent project in breast cancer this is precisely what happened. When studying the action of a known drug in the context of breast cancer we actually stumbled over a new target of this drug.
Q: What are the most important lines of research that have developed over the last five to ten years?
SN: As pharmacogenomics is about the intersection between genetics on one hand and pharmaceuticals, drugs, on the other, there has actually been a few major things happening. Particularly on the side of genomics what we have seen in the last years is what we call the unfolding of the genetic landscape of cancer. By now for the majority of cancers we actually know what the genetic variation is and on top of that for individual patients we can now identify those genetic variants. So we now have the tools to essentially map the landscape of each individual patient. On the other side, in the drug discovery area, we have seen an enormous increase in the number of targeted agents, meaning drugs that are very precisely designed to inhibit particular targets in the cell. These two things that have come of age in the last five to ten years allow us now to really start looking at this intersection between genetics and pharmaceuticals.
Q: Why does your line of research matter and why should we put money into it?
SN: It matters because we are talking about patients that are prescribed drugs that don’t work for them, and often they suffer side-effects of these drugs, which can be quite horrific, particularly in the context of cancer. That also comes with an enormous waste when the patients don’t benefit from these drugs as it also puts an enormous pressure on the health care system, particularly with the rising cost of these very expensive targeted agents. What we try to do with pharmacogenomics is better match patient with the best drug and thereby save a lot of time and money.
Q: How does your research fit into translational medicine within the department?
SN: It fits well because even though the stuff that we do in the lab is fairly basic, the implications of the work is very translational. For instance, we have been working on a project in lung cancer where we discovered that a drug used in melanoma may in a very specific genetic context in lung cancer work beneficially. Here is research that has direct translational implications and what we would like to do now is a clinical trial to test this hypothesis in patients.