Recent developments in targeted therapies
Dr Stephen Nimer - University of Miami, Miami, USA
There’s been a huge focus now on sequencing the DNA of cancers, of tumours, and what we’ve learned is the tremendous heterogeneity among different patients’ cancer. So we actually believe that everyone’s cancer is pretty unique and some research which is not going to be presented at this meeting but which is going on at Sylvester at the University of Miami is trying to use biostatistical methods to actually calculate just how similar or different everyone’s cancer is. It turns out, using mathematical formulae, that people’s cancers are quite different. So if we look at the mutational schema this would suggest that everyone may need a different type of therapy and that’s not practical. So what we have to find and what’s very exciting is the notion that mutations in a specific class of molecules may lead to a specific type of therapy. Sometimes this is referred to as synthetic lethality where if there’s a mutation in gene A and you block pathway B then you can kill the cancer cell. But in a normal cell when you block pathway B, because the normal cell doesn’t have mutation A, there’s no effect at all of the therapy. So this is a way of developing targeted precision medicine based on the presence of more than one abnormality.
So, although everyone may have a different mutation in gene A, if we can identify what it is that gene B or pathway B we may be able to use one of a handful of therapies broadly against patients with cancer as opposed to having to come up with thousands of different combinations of treatment.
The other area where we’re developing some more precision medicine is understanding how different patients metabolise drugs. So for both chemotherapy, for immunotherapy and for some of the targeted therapies it turns out that your genetic background may determine how you metabolise drugs. So now that we get this information also when we sequence DNA in a cancer it can help us guide dosing or even choice of agents.
In terms of things coming out of this year’s ASCO conference has there been anything in related fields?
One of the most exciting aspects is the convergence between some of the precision medicine efforts and immunotherapy. So we believe now that for some cancers they’re a very good target of immunotherapy because there are so many mutations and that the cancer cells present what we would call neoantigens to the immune system. What we’re now trying to do is toy develop epigenetic drugs that can expose more neoantigens and can make immunotherapy more effective and try to identify strategies for improving one area of these three, the triumvirate – immunotherapy, epigenetic therapy, targeted therapies, we are learning new ways to combine these. I think that’s probably what’s most exciting about this meeting and future meetings, to see this come to reality.
Checkpoint inhibitory therapy is also right at that crossover as well.
Yes. In fact, when I refer to immunotherapy the checkpoint blockade is an important component of that and then there’s all the cellular therapies which we’re hearing about – CAR T-cells and other modified cells, NK cells, even NKT cells perhaps in the future.
Is there anything that you’d like to add or any conclusion that you’d like to offer?
There are now so many new drugs and so many new options for patients and we’re extending people’s lives in important ways. The most exciting thing about immunotherapy is the idea that we may be curing patients of cancers that were previously incurable and that’s the real challenge for us is to be able to cure more patients with cancer.