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Int. J. Mol. Sci. 2018, 19(2), 394; https://doi.org/10.3390/ijms19020394

Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas

1
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
2
Medical Research Scholars Program, Office of Clinical Research Training and Medical Education, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
3
Leidos Biomedical Research, Inc., Frederick, MD 21704, USA
4
NIH Comparative Biomedical Scientist Training Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Received: 23 December 2017 / Revised: 19 January 2018 / Accepted: 22 January 2018 / Published: 30 January 2018
(This article belongs to the Special Issue Animal Models of Melanoma)
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Abstract

Melanoma remains mostly an untreatable fatal disease despite advances in decoding cancer genomics and developing new therapeutic modalities. Progress in patient care would benefit from additional predictive models germane for human disease mechanisms, tumor heterogeneity, and therapeutic responses. Toward this aim, this review documents comparative aspects of human and naturally occurring canine melanomas. Clinical presentation, pathology, therapies, and genetic alterations are highlighted in the context of current basic and translational research in comparative oncology. Somewhat distinct from sun exposure-related human cutaneous melanomas, there is growing evidence that a variety of gene copy number alterations and protein structure/function mutations play roles in canine melanomas, in circumstances more analogous to human mucosal melanomas and to some extent other melanomas with murine sarcoma viral oncogene homolog B (BRAF), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS), and neurofibromin 1 tumor suppressor NF1 triple wild-type genotype. Gaps in canine genome annotation, as well as an insufficient number and depth of sequences covered, remain considerable barriers to progress and should be collectively addressed. Preclinical approaches can be designed to include canine clinical trials addressing immune modulation as well as combined-targeted inhibition of Rat Sarcoma Superfamily/Mitogen-activated protein kinase (RAS/MAPK) and/or Phosphatidylinositol-3-Kinase/Protein Kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signal transduction, pathways frequently activated in both human and canine melanomas. Future investment should be aimed towards improving understanding of canine melanoma as a predictive preclinical surrogate for human melanoma and for mutually benefiting these uniquely co-dependent species. View Full-Text
Keywords: comparative genomics; clinical trial design; precision medicine; dogs; translational research; drug development; immunotherapy; signal transduction; kinase inhibition comparative genomics; clinical trial design; precision medicine; dogs; translational research; drug development; immunotherapy; signal transduction; kinase inhibition
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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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Hernandez, B.; Adissu, H.A.; Wei, B.-R.; Michael, H.T.; Merlino, G.; Simpson, R.M. Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas. Int. J. Mol. Sci. 2018, 19, 394.

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