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Improving human cancer therapy through the evaluation of pet dogs

Abstract

Comparative oncology clinical trials play an important and growing role in cancer research and drug development efforts. These trials, typically conducted in companion (pet) dogs, allow assessment of novel anticancer agents and combination therapies in a veterinary clinical setting that supports serial biologic sample collections and exploration of dose, schedule and corresponding pharmacokinetic/pharmacodynamic relationships. Further, an intact immune system and natural co-evolution of tumour and microenvironment support exploration of novel immunotherapeutic strategies. Substantial improvements in our collective understanding of the molecular landscape of canine cancers have occurred in the past 10 years, facilitating translational research and supporting the inclusion of comparative studies in drug development. The value of the approach is demonstrated in various clinical trial settings, including single-agent or combination response rates, inhibition of metastatic progression and randomized comparison of multiple agents in a head-to-head fashion. Such comparative oncology studies have been purposefully included in the developmental plan for several US FDA-approved and up-and-coming anticancer drugs. Challenges for this field include keeping pace with technology and data dissemination/harmonization, improving annotation of the canine genome and immune system, and generation of canine-specific validated reagents to support integration of correlative biology within clinical trial efforts.

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Fig. 1: Comparative molecular features of canine and human osteosarcoma.
Fig. 2: Comparative aspects of immune cell subsets in dogs and humans.

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Acknowledgements

The authors thank W. Hendricks, P. Choyke and N. Mason for their critical review of this manuscript. They thank J. Meyer for artistic input and technical assistance with the figures, and A. Cherukuri for assistance with manuscript preparation. This work was supported by the Intramural Program of the National Cancer Institute, National Institutes of Health (NIH; Z01-BC006161). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.

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A.K.L. researched data for the article and wrote the article. A.K.L. and C.N.M. both made substantial contributions to discussion of content and reviewed/edited the manuscript before submission.

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Correspondence to Amy K. LeBlanc.

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Nature Reviews Cancer thanks M. Breen, S. Day and T. Fan for their contribution to the peer review of this work.

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Related Links

American Veterinary Medical Association: https://ebusiness.avma.org/aahsd/study_search.aspx

Brazilian Veterinary Cancer Society: https://abrovet.org.br

Cancer Moonshot Immunotherapy Trials Network in Comparative Oncology: https://dctd.cancer.gov/NewsEvents/20190327_canine_immunotherapy.htm

Clinical and Translational Science Award One Health Alliance: https://ctsaonehealthalliance.org

Comparative Oncology Program: https://ccr.cancer.gov/Comparative-Oncology-Program

Consortium for Canine Comparative Oncology: https://www.c3oncology.org

European Society of Veterinary Oncology: https://www.esvonc.com/Esvonc/national-veterinary-oncology-societies

Integrated Canine Data Commons: https://caninecommons.cancer.gov/#/

Japan Veterinary Cancer Society: http://www.jvcs.jp/english/

PRECINCT (Pre-medical Cancer Immunotherapy Network for Canine Trials): https://www.precinctnetwork.org

PRECINCT Project Synopses: https://www.precinctnetwork.org/project-synopses

Veterinary Cancer Society: www.vetcancersociety.org

Glossary

Array-based comparative genome hybridization

A genomic DNA hybridization technique that allows high-resolution analysis of copy number changes between two populations (such as normal versus tumour DNA).

Homologous recombination DNA repair pathway

A repair mechanism in which an identical or nearly identical DNA sequence from a homologous chromosome is used as a template for the repair of a DNA break.

Mismatch repair

A strand-specific mechanism for editing mismatched bases inserted in the daughter strand during DNA replication. This damage is repaired by recognition of the deformity caused by the mismatch.

Blood–brain barrier

An interconnected network of capillaries that carries blood to the brain and spinal cord, but also blocks the passage of certain harmful substances.

Convection-enhanced delivery

A technique that generates a pressure gradient at the tip of an infusion catheter to facilitate delivery of therapeutics to the central nervous system.

Volume of drug distribution

A pharmacokinetic parameter that represents the theoretical volume into which a drug is distributed throughout the body based on solubility, charge, size and so forth.

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LeBlanc, A.K., Mazcko, C.N. Improving human cancer therapy through the evaluation of pet dogs. Nat Rev Cancer 20, 727–742 (2020). https://doi.org/10.1038/s41568-020-0297-3

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