A Little Help from Man's Best Friend

My last post suggested that some new drugs don't make it to market because the existing trials process doesn't provide critical information that can be used to optimise the trial design and reveal the true potential of the drugs being tested.

A change in the existing trial process would have serious legal and ethical issues to contend with, and so is unlikely to occur. It can however be supplemented in such a way that streamlines the process, more accurately determines the effect of a cancer drug and can reduce the time to market. That solution is dogs. These are not your typical animal experiments, such as the rat or mouse models of cancer, in which the animal often lacks a fully functional immune system and the cancer itself is a cross-species 'xenograft' implant. Its fairly easy to see how these models do not accurately represent the type of cancer that occurs naturally in the body, and that's where the dogs come in.

In the USA up to 6 million pet dogs are diagnosed with cancer every year. Canine cancer is surprisingly similar to human cancer. Dogs get the same types of cancers as humans, they are genetically similar to humans and crucially, large scale genomic analyses of canine tumors have shown that there are no differences in the genetic mechanisms of the cancer. The other similarities in canines include their size and the fact that they possess fully functioning immune systems. The similarity between dogs and humans is so close that most existing drugs can be used to treat equivalent diseases in both species.

Naturally dog owners are keen to pursue any therapies that may prevent the death of their pet. Fortunately they can, in the USA the National Cancer Institute operates a network of animal hospitals, fully equipped with state of the art imaging technologies to accurately diagnose and monitor canine cancer. Similar work is carried out at the Roslin Institute in Scotland. These centres are used to test new therapies on the plentiful supply of canine patients following Good Clinical Practice guidelines and central reporting of dangerous side effects not too dissimilar to those in place to protect human patients.

The canine trials can start providing detailed information on the mechanisms of the drugs action before even the Phase I trial in humans starts. Information such as genetic profiles for which the drug is ineffective or blood markers that can be used to determine successful responses in advance of significant tumor reduction. These can all be translated to human systems and used to better design the human trials. These types of biomarkers are not often discovered until around Phase II of human trials, and are usually validated during phase III. Having them in place for Phase I is very useful as they can be validated in the early phases and used to optimise the later more expensive and time consuming phases. For example selective enrolment of patients who have the genetic or biochemical profile compatible with the drug would make the trial more decisive, while freeing other patients to pursue other therapies with more likelihood of success for them. Another benefit is instead of waiting years to determine the survival of the patient and therefore whether the drug was effective, biomarkers that provide advanced indicators of survival could provide that information in months, drastically reducing the length of the trial and therefore the costs.

Comparative Oncology such as this has the potential to give us a much more detailed understanding of the drugs we are testing and should help bring more new drugs to market and quicker. Cancer is a complex and diverse disease that will not be overcome by a single therapy alone, we will need to use combinations of therapies specifically targetted to a patients personal disease to attack it from several fronts. Therefore understanding each cancer type and each drug as much as is technically possible will be critical in determining potential drug synergies and creating successful recipes for treatment.