The domestic dog has become increasingly useful as a comparative spontaneous
cancer model to study genetic and environmental risk factors as well as for easing the
transition between rodent and human clinical trials for novel cancer therapies. The many
similarities between various cancer types affecting humans and dogs and the
spontaneous development of these cancers in immune competent canine individuals
living in a shared environment with us suggest a common aetiology. The shorter lifespan
of dogs and the shorter time to relapse after cancer treatment allows data regarding
efficacy, short and long term toxicity and side effects of novel cancer drugs to be
generated in years rather than decades as in human clinical trials.
However, certain limitations need to be overcome to make full use of the dog model.
Slightly different classification systems for common cancers limit translation of data and
clinical outcome from dog to human. The canine genome and annotation, especially that
of complex immune gene families, could be improved to allow a more careful and correct
comparison with the human genome and immune response, a key factor in cancer
development and treatment.
Using novel long-read sequencing techniques, we will generate a platinum CanFam4.0
genome and improved information of both gene and variant annotation for an old healthy
female German shepherd. In addition, we will specifically focus on canine mammary
tumors, lymphoma and osteosarcoma where improved models would benefit human
studies, and the canine forms are diverse and only partly characterized. Since the
molecular sub-classifications used in human cancers are not yet used for these canine
cancers, we plan to characterize these tumor types in the dog population using several
approaches to meet human standards. We will further set up a Scandinavian-wide
veterinary oncology network for research collaboration, increased use of the dog as a
model. We will perform repeated blood sampling from dogs with malignant mammary
tumors to allow the study of tumor evolution and progression. All of this work will lay the
groundwork to enable more useful and efficient future clinical trials.