Will we win the battle against cancer by finding a cure? It’s the time-old question for cancer researchers, posed most recently by an excellent article in the Observer on drug resistance in cancer treatment that quoted three of our scientists here at The Institute of Cancer Research, London.
It’s a really interesting piece and I do recommend that you read it if you are interested in the latest thinking on how best to treat cancer. The article tells the story of cancer drug resistance really nicely, and how genetic differences between different cells within a tumour can lead to cancers recurring when drug-resistant cells re-establish the tumour after an initial treatment response.
The article also raises a point which I am keen to talk more about here. It features a patient who has been in treatment for prostate cancer since 2004, and introduces the concept of treating cancers as a chronic condition, with ongoing treatment regimes allowing some patients to survive for many years after diagnosis.
This concept of long-term treatment of cancer as a chronic disease often sparks debate. Should we be thinking of cancer in this way and concentrating on developing treatments which extend patients’ lives, or should we be focusing on finding ‘a cure’ for cancer?
Our mission here at The Institute of Cancer Research (ICR) is to improve patients’ lives by making the discoveries that defeat cancer, and for us, the answer has got to be both.
It is unlikely there will ever be one ‘magic bullet’ cure for cancer. What we term cancer is made up of more than 200 different diseases, and there is considerable genetic diversity between different tumours of the same type, and even within a tumour. Cancers have for a very long time been categorised according to the tissue they originate in – in the terms that we’re used to hearing, such as breast cancer or prostate cancer – and also sub-typed by how they appear when looked at down the light microscope. But now they are also classified in much more detail at a molecular level, depending on the particular genetic cause that has led to the cancer developing.
This means there are many thousands of cancer sub-types. In fact each individual cancer is genetically unique – which supports the approach known as ‘personalised medicine’.
With this enormous diversity of tumour types and causes, it is unlikely that there will ever be one cure for cancer, but advances in our understanding of cancer genetics and biology, new medicines and the rational design of treatment combinations are increasing the armoury we have at our disposal for defeating cancer.
Targeted cancer treatments, rather than killing all cells including healthy ones, as with traditional cytotoxic chemotherapy, exploit the specific cancer-causing faults in each tumour. Over 100 targeted cancer drugs have now been approved for patient use and they represent a significant step forward in cancer treatment. The drug imatinib (marketed as Glivec), a targeted cancer treatment aimed a particular gene defect in chronic myeloid leukaemia, has led to the number of people dying from the disease plummeting by 80 per cent. In the case of malignant melanoma – an aggressive skin cancer – patients with the form of the disease caused by a faulty BRAF gene are treated with the targeted drug vemurafenib and show remarkable improvement. But as the Observer article describes, this only lasts on average for around six months or so.
The variation between cells within an individual tumour means some cancer cells will survive the initial treatment, and these will be the ones that go on to re-establish the tumour, this time resistant to the original treatment. Whereas in Darwinian evolution there is selection for the survival of the fittest, in the case of cancer cells, as described in the article by Professor Paul Workman, the ICR’s Deputy Chief Executive, "it is all about the survival of the nastiest".
But this doesn’t mean that targeted drugs are not worth pursuing. Researchers at the ICR and elsewhere have been investigating combination treatments which use several drugs at the same time or in close sequence, and most importantly are using rational combinations of drugs to hit different cancer pathways at once, knocking out all the tumour sub-populations. With this approach, tumours are less likely to be able to escape the effects of the drugs.
Researchers have known for a long time that tumours are heterogeneous and that combination treatments are very effective. What has changed recently is our far greater understanding of the underlying genetic diversity and also our ability to use precision drug combinations that are targeted to the evolving pattern of genetic changes in individual patients.
So to come back to the question – should we be designing drugs to extend patient survival, but that on their own may not be the ultimate cure for cancer? The answer is definitely yes.
A drug which may currently increase patient survival by six months or more may end up being part of a drug treatment cocktail that results in years of chronic management or that ends up being the cure for a particular type of tumour. And in the meantime, those six months will be welcome to patients and their families.
Professor Workman told me: “I don’t think people should worry that we are aiming for short-term gains or chronic management at the expense of cure. At The Institute of Cancer Research we are aiming to improve and extend the lives of all cancer patients as much as possible. And the approaches we are taking should achieve both. By extending survival we are working towards cure.”
Every step we make that improves patient survival – whether by increasing our understanding of the genetic causes of cancer, designing new drugs that target faulty cancer genes, or putting them together into new treatment combinations – is progress towards eventual cures. And along the way, the advances we make are prolonging survival times. Survival rates for cancers have doubled since the 1970s. We are constantly increasing our understanding of different tumours and how to treat them. Genetically targeted combination therapy may be the next step change in our progress as we learn how to control cancer – and in turn how to cure it.
comments powered by