A solid tumour is the perfect example of a complex adaptive system at work. It is an ecosystem with competitive and cooperative networks of cells at play. This is one of the reasons why cancer is so difficult to treat.
Historically, the approach has been to blast tumours with the most toxic drugs at our disposal – cytotoxic chemotherapies. These are aimed at causing massive cell death in populations of rapidly dividing cells. Of course, there’s a good degree of collateral damage too, as anyone who’s had chemotherapy can attest – those toxic drugs don’t distinguish between rapidly dividing tumour cells and rapidly dividing cells in the immune system, hair follicles, stomach lining and so on.
We’ve pretty much done the same thing with radiotherapy, blasting the tumour with radiation in the hope that it kills the cancer cells, but again we have non-cancer cells in the neighbourhood that also get fried along the way.
One response has been to look at how we can improve our aim. Oncology has been searching for “magic bullets” for a long time now. As our understanding of the molecular basis of cancer has developed in the last thirty years, so has the identification of these targets.
All of which brings us to the present day.
News of one new type of targeted approach emerged this week – using genetically altered stem cells taken from bone marrow to destroy cancer cells growing in lungs.
But we are also starting to see “targeted therapies” find their way from pharma labs to the clinic – with great fanfare and huge amounts of hope that we’ve cracked it this time. That’s the theory, anyway.
In practice we have seen some spectacular results – tumours regress, patients go into remission and drug companies can start to recoup the billions spent on R&D. Except that in many cases, those regressions are temporary – which brings us back to the evolutionary nature of cancer. Nature is extremely adaptive, and our bodies have multiple redundant networks at work, with all kinds of complex feedback loops and connections that we barely understand. If we shut off one pathway, then another one often comes into play.
But what if there’s a different way? What if instead of looking for combinations of extremely well-targeted agents (which are both new and incredibly, incredibly expensive), we look to see what we’ve already got in the pharmacy? This is the field of drug repurposing, which offers a radically different approach to the search for anti-cancer drugs. At this point I should declare an interest – this is the area of research I work in as part of the Repurposing Drugs in Oncology project.
In contrast to the newer generation of targeted therapies, many of our older drugs are considered "dirty drugs". Personally I think of these as multi-targeted agents, in contrast to the mono-targeted agents coming out of the drug pipelines. The vast majority of these drugs are non-cancer drugs – they were developed for a wide range of illnesses and conditions – including antibiotics, antifungals, treatments for high blood pressure, elevated cholesterol, antidepressants and so on.
So how is it possible that commonly prescribed non-cancer drugs, of the types available in your local pharmacy, can be active against cancer? Part of the answer comes back to the understanding that cancer is not simply a homogeneous mass of delinquent cells. The tumour ecosystem contains a surrounding microenvironment of stromal cells, immune cells, sprouting blood vessels and so on.