For this first post of 2012 I want to start on a positive note by highlighting an interesting and relevant piece of research from Italy. Chemoresistance is the term used to describe the process whereby cancer cells become resistant to chemotherapy. Unfortunately this is a serious and widespread problem, right across the spectrum of cancer types. Tumours that regress quickly from the initial rounds of chemo, sometimes shrinking away to nothing almost, suddenly seem to bounce back, growing again and shrugging off repeated rounds of the chemo that seemed to knock them out. In many cases these resistant cancer cells become ‘multi-drug resistant’, which means that second and third line chemotherapy treatments also have little or no effect. So, finding a way of reversing this resistance is an important aim in cancer research, and one which is clinically relevant across most kinds of cancer.
It’s this problem that a team of researchers and clinicians in Italy have tackled in a clinical trial. Building on work previously done in the laboratory, Stefano Fais and his co-workers carried out a clinical trial on cats and dogs (now called ‘companion animals’ rather than pets!) with cancers that were resistant to standard chemotherapy. Don’t for one minute think that because the patients were animals that this is not relevant research. Cancers in cats and dogs are much closer to human cancers than cancers in rats and mice. In some types of disease, such as osteosarcoma, the disease acts in exactly the same way that it does in people, and is treated with the same drugs and treatments.
These animals were treated with the common anti-acid drug lansoprazole at high doses – a drug that is available over the counter in the UK – along with the chemotherapy drugs that often fail due to the development of chemoresistance. The response of these animals was compared to another set of animals that had the conventional chemo-only treatment (it was the owners of the animals who decided to stick to the conventional treatments only).
The results were very clear. In the lansoprazole treated group, more than two thirds of animals showed partial or complete responses, compared to 17%of animals in the chemo-only group who showed short-lived partial responses. What’s more, even in the non-responders in the lansoprazole group, the owners of the animals indicated that their pets showed improved quality of life – less pain, less weight loss, greater agility etc.
The conclusion is clear, that taking high dose lansoprazole stopped cancers developing chemoresistance in about two thirds of the treated animals. In these animals the chemo regressed the cancers partially or completely. In the animals treated with lansoprazole even those animals that did not show a tumour response, the lansoprazole still managed to improve quality of life. Particularly noteworthy is that the dogs with osteosarcoma showed improvements related to a reduction in pain – and this is a form of pain that does not normally respond well to normal pain relief drugs.
The paper by Dr Fais and colleagues goes into some detail on the presumed mechanisms for these results – mostly related to the fact that lansoprazole (and other similar proton pump inhibitor drugs like omeprazole) are targeted at acidic environments in the body, and cancers are known for producing a very acidic microenvironment.
Aside from the direct clinical relevance (and human clinical trials can be started off the back of this one), the paper and the trial are interesting for a number of other reasons. Firstly, this is yet another good example of good research, going from solid theoretical and laboratory data, to work in rats and mice and now in cats and dogs and now on to humans. Secondly, this study uses a cheap and readily available drug that is widely used, thus short circuiting many years of safety testing. It is part of a welcome trend in using existing drugs for tackling cancer and cancer-related conditions – other notable examples include the anti-diabetic drug metformin, beta blockers, celecoxib and aspirin. Finally, as with many of the other off-label drugs listed, the target here isn't cancer cells directly, but the tumour microenvironment. Without a supportive microenvironment, cancer cannot thrive and prosper, which is exactly what we want. In this case, by attacking the microenvironment it means that existing chemotherapy drugs can work more effectively and kill the cancer cells.
The hope now is that these results can be replicated in a wide range of human cancers, making them susceptible again to the chemotherapy that all too often stops working.
The full paper (which is published open access) is here: http://www.translational-medicine.com/content/9/1/221/abstract