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Vet. Sci. 2016, 3(1), 3; doi:10.3390/vetsci3010003

Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach

1
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
2
Department of Surgery, University of Minnesota Medical School, Moos Tower, 11-212420 Delaware Street, S.E.; MMC 195, Minneapolis, MN 55455, USA
3
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55455, USA
4
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA
5
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Duncan C. Ferguson and Margarethe Hoenig
Received: 19 November 2015 / Revised: 23 December 2015 / Accepted: 11 January 2016 / Published: 18 January 2016
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
View Full-Text   |   Download PDF [223 KB, uploaded 18 January 2016]

Abstract

Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its recurrence after initial therapy is a major factor for the poor outcomes. It is thought that most human and canine patients have at least microscopic metastatic lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater frequency and shares many biological and clinical similarities with osteosarcoma in humans. From a genetic perspective, osteosarcoma in both humans and dogs is characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Similar molecular abnormalities have been observed in human and canine osteosarcoma. For instance, loss of TP53 and RB regulated pathways are common. While there are several oncogenes that are commonly amplified in both humans and dogs, such as MYC and RAS, no commonly activated proto-oncogene has been identified that could form the basis for targeted therapies. It remains possible that recurrent aberrant gene expression changes due to gene amplification or epigenetic alterations could be uncovered and these could be used for developing new, targeted therapies. However, the remarkably high genomic complexity of osteosarcoma has precluded their definitive identification. Several advantageous murine models of osteosarcoma have been generated. These include spontaneous and genetically engineered mouse models, including a model based on forward genetics and transposon mutagenesis allowing new genes and genetic pathways to be implicated in osteosarcoma development. The proposition of this review is that careful comparative genomic studies between human, canine and mouse models of osteosarcoma may help identify commonly affected and targetable pathways for alternative therapies for osteosarcoma patients. Translational research may be found through a path that begins in mouse models, and then moves through canine patients, and then human patients. View Full-Text
Keywords: osteosarcoma; comparative oncology; microRNAs; prognosis; canine osteosarcoma osteosarcoma; comparative oncology; microRNAs; prognosis; canine osteosarcoma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Varshney, J.; Scott, M.C.; Largaespada, D.A.; Subramanian, S. Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach. Vet. Sci. 2016, 3, 3.

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