Malignant Histiocytosis: Looking for a Cure

12/01/2010

NickyMalignant histiocytosis (MH) is an extremely aggressive form of cancer that is a major cause of death for Bernese Mountain dogs. It also affects Flat-Coated Retrievers, Golden Retrievers, and Rottweilers. The tumors that MH causes eventually infiltrate many of a dog’s organs, and the disease is always fatal.

The median survival time for malignant histiocytosis is only 2-4 months. Because of its tendency to spread rapidly through the body, traditional cancer treatments such as radiation and surgery are generally ineffective in dogs with MH. Even chemotherapy has historically been shown to have only limited effect. There is hope for the future; however, as preliminary studies of a new form of treatment have shown some real promise.

Although it is difficult to imagine, all cancer cells were once healthy parts of the body. In the case of MH, the cells that make up the tumors would normally have become either dendritic cells or macrophages. Those are both types of phagocytic cells – white blood cells that can engulf foreign bodies and destroy them. Originating in the bone marrow, at maturity such cells are an important tool in the immune system’s fight against disease.

Interestingly, the very trait that makes phagocytic cells so good at attacking foreign invaders could also be the key to fighting this devastating cancer. Like the cells that give rise to them, MH tumor cells are phagocytic, and researchers from Colorado State University may have found a way to use that trait to aid in their destruction.

In a new study funded by the AKC Canine Health Foundation, Dr. Steven Dow and his colleagues have looked at the effects of packaging a chemotherapeutic agent, clodronate, in a way that makes it enticing for phagocytic cells to "eat." This particular way of delivering clodronate had already been shown to effectively lower the number of macrophages in mice, and it seemed like it could be a new way to attack the normally treatment resistant tumors of MH.

The packaged drug, liposomal clodronate (LC), seems to be living up to its potential. Through a series of experiments, the researchers discovered that while clodronate could efficiently kill off a number of different tumor cell lines, liposomal clodronate was only an effective treatment for tumor cells that could take it in through phagocytosis. Even more promisingly, the packaged drug was better at killing the MH tumor cell lines than the free drug – suggesting that when used it dogs with this cancer, it might work where other chemotherapeutics had failed.

When the researchers tested the efficacy of LC in five dogs with treatment resistant MH tumors they found that even the sickest of the dogs tolerated the treatment well. Even better, two of the five dogs showed some improvement in their tumors. Why only two? When the scientists looked at three different MH tumor cell lines they found that some were better at phagocytosis than others – and that those tumors were more susceptible to LC treatment. If the dogs’ tumor cells were similarly variable in how efficiently they could uptake the packaged drug, it could explain why the treatment only worked in some animals.

There was one potentially discouraging note to the research. Neither of the two Bernese Mountain Dogs in the study responded to treatment with LC. Unfortunately, with such a small number of dogs in the test group, it was impossible to tell if that was simply due to the particular dogs in question or if it reflected a fundamental difference in the MH tumors of the most commonly affected breed.

Hopefully future research will provide more answers. Developing new treatments for malignant histiocytosis has the potential to not only improve the lives of the many dogs who are affected by this cancer but also the lives of the humans who are affected by a similar cancer known as Langerhans cell histiocytosis.

This work was funded by AKC Canine Health Foundation Grant 1152.

Scientific publications:

Hafeman, S., et al., Evaluation of liposomal clodronate for treatment of malignant histiocytosis in dogs. Cancer Immunology, Immunotherapy, 2010. 59(3): p. 441-452.

 

 

 

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