{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:20:55Z","timestamp":1787862055599,"version":"build-2784847793"},"reference-count":73,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Talent Fund of China Agricultural University Veterinary Teaching Hospital (Beijing Zhongnongda Veterinary Hospital Co., Ltd.)","award":["1051-2221002"],"award-info":[{"award-number":["1051-2221002"]}]},{"name":"Talent Fund of China Agricultural University Veterinary Teaching Hospital (Beijing Zhongnongda Veterinary Hospital Co., Ltd.)","award":["202006170058"],"award-info":[{"award-number":["202006170058"]}]},{"name":"China Scholarship Council (CSC)","award":["1051-2221002"],"award-info":[{"award-number":["1051-2221002"]}]},{"name":"China Scholarship Council (CSC)","award":["202006170058"],"award-info":[{"award-number":["202006170058"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Canine malignant melanoma (CMM) is highly aggressive and mostly located in the oral cavity. CMM is the predominant type of canine oral malignancy and shows striking homologies with human mucosal melanoma. In comparative oncology, canine oral melanomas (COMs), as spontaneous tumor models, have the potential to acquire a unique value as a translational model of rare human melanoma subtypes. This review aims to provide a comprehensive summary of targeted therapies for canine malignant melanoma and to enrich the field of comparative oncology. Following the PRISMA guidelines, a comprehensive literature search was conducted across databases for studies from 1976 to April 2024. Studies were selected based on their relevance to targeted treatments. A total of 30 studies met the inclusion criteria. Based on the treatment approaches, the studies were further categorized into immunotherapies, small molecule signaling inhibitors, indirect kinase inhibitors, and other alternative strategies. Some treatments have been shown to result in stable disease or partial response, accounting for 29% (monoclonal antibody) and 76.5% (micro-RNA therapies) in clinical trials. Moreover, in vitro experiments of small molecule inhibitors, including cell signaling inhibitors and indirect kinase inhibitors, have shown the potential to be an effective treatment option for the development of therapeutic strategies in canine malignant melanoma. The observed response in in vitro experiments of CMM (particularly the oral and certain cutaneous subtypes) to drugs used in the treatment of human melanoma underlines the resemblance to human melanoma, therefore supporting the notion that CMM may be a valuable model for understanding rare human melanoma subtypes and exploring potential therapeutic avenues in preclinical trials. Finally, this literature review serves as a valuable resource for the development of therapeutic strategies for CMM and highlights the potential for translating these findings to human cancer treatment.<\/jats:p>","DOI":"10.3390\/ijms251910387","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T03:44:13Z","timestamp":1727408653000},"page":"10387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Comparative Oncology of Canine Malignant Melanoma in Targeted Therapy: A Systematic Review of In Vitro Experiments and Animal Model Reports"],"prefix":"10.3390","volume":"25","author":[{"given":"Xiaohui","family":"He","sequence":"first","affiliation":[{"name":"Department of Small Animal Medicine, College of Veterinary Medicine, China Agriculture University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7722-2136","authenticated-orcid":false,"given":"Yu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"},{"name":"Department of Medicine, Clinic III, Hematology, Oncology and Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine, College of Veterinary Medicine, China Agriculture University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"He","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine, College of Veterinary Medicine, China Agriculture University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Nolte","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-7986","authenticated-orcid":false,"given":"Hugo","family":"Murua Escobar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Clinic III, Hematology, Oncology and Palliative Medicine, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine, College of Veterinary Medicine, China Agriculture University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/pcmr.12170","article-title":"Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas","volume":"27","author":"Gillard","year":"2014","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Prouteau, A., and Andr\u00e9, C. (2019). Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison. Genes, 10.","DOI":"10.3390\/genes10070501"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/pcmr.12185","article-title":"Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma","volume":"27","author":"Simpson","year":"2014","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_4","first-page":"e5505","article-title":"Spontaneously occurring melanoma in animals and their relevance to human melanoma","volume":"252","author":"Brenn","year":"2020","journal-title":"J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bongiovanni, L., Brachelente, C., Dow, S., and Bergman, P.J. (2022). Editorial: Canine melanoma in comparative oncology: Translate research advances to develop new diagnostic and therapeutic options. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.1127527"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.7150\/thno.55760","article-title":"Molecular targets for anticancer therapies in companion animals and humans: What can we learn from each other?","volume":"11","author":"Kromhout","year":"2021","journal-title":"Theranostics"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hardwick, L. (2021). A Comparative View on Molecular Alterations and Potential Therapeutic Strategies for Canine Oral Melanoma. Vet. Sci., 8.","DOI":"10.3390\/vetsci8110286"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tvjl.2015.10.008","article-title":"Cancer immunotherapy in veterinary medicine: Current options and new developments","volume":"207","author":"Regan","year":"2016","journal-title":"Vet. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1292\/jvms.23-0204","article-title":"Second era of molecular-targeted cancer therapies in dogs","volume":"85","author":"Maeda","year":"2023","journal-title":"J. Vet. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1939-1676.1999.tb02173.x","article-title":"The Molecular Basis of Canine Melanoma: Pathogenesis and Trends in Diagnosis and Therapy","volume":"13","author":"Modiano","year":"1999","journal-title":"J. Vet. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hernandez, B., Adissu, H.A., Wei, B.-R., Michael, H.T., Merlino, G., and Simpson, R.M. (2018). Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020394"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1046\/j.1445-2197.2003.02748.x","article-title":"Methodological index for non-randomized studies (minors): Development and validation of a new instrument","volume":"73","author":"Slim","year":"2003","journal-title":"ANZ J. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.2460\/ajvr.70.2.263","article-title":"Activation of the AKT and mammalian target of rapamycin pathways and the inhibitory effects of rapamycin on those pathways in canine malignant melanoma cell lines","volume":"70","author":"Kent","year":"2009","journal-title":"Am. J. Vet. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s00262-005-0025-6","article-title":"Development of an allogeneic whole-cell tumor vaccine expressing xenogeneic gp100 and its implementation in a phase II clinical trial in canine patients with malignant melanoma","volume":"55","author":"Alexander","year":"2006","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"London, C.A., Bernabe, L.F., Barnard, S., Kisseberth, W.C., Borgatti, A., Henson, M., Wilson, H., Jensen, K., Ito, D., and Modiano, J.F. (2014). Preclinical Evaluation of the Novel, Orally Bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in Spontaneous Canine Cancer: Results of a Phase I Study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087585"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/jvp.12336","article-title":"Selective growth inhibition by suppression of F1Fo ATPase in canine malignant melanoma cell lines","volume":"40","author":"Kuroki","year":"2017","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1292\/jvms.66.1437","article-title":"Establishment and Characterization of Four Canine Melanoma Cell Lines","volume":"66","author":"Inoue","year":"2004","journal-title":"J. Vet. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.tvjl.2014.07.012","article-title":"6-Bromoindirubin-3\u2032oxime (BIO) decreases proliferation and migration of canine melanoma cell lines","volume":"205","author":"Chon","year":"2015","journal-title":"Vet. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1292\/jvms.63.83","article-title":"Effect of retinoids on growth inhibition of two canine melanoma cell lines","volume":"63","author":"Ohashi","year":"2001","journal-title":"J. Vet. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.tvjl.2017.02.001","article-title":"Molecular investigation of the direct anti-tumour effects of nonsteroidal anti-inflammatory drugs in a panel of canine cancer cell lines","volume":"221","author":"Yoshitake","year":"2017","journal-title":"Vet. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/vco.12778","article-title":"Atorvastatin preferentially inhibits the growth of high ZEB-expressing canine cancer cells","volume":"20","author":"Ishikawa","year":"2022","journal-title":"Vet. Comp. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/pcmr.12512","article-title":"Synergistic targeted inhibition of MEK and dual PI3K\/mTOR diminishes viability and inhibits tumor growth of canine melanoma underscoring its utility as a preclinical model for human mucosal melanoma","volume":"29","author":"Wei","year":"2016","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Breit, M.N., Kisseberth, W.C., Bear, M.D., Landesman, Y., Kashyap, T., McCauley, D., Kauffman, M.G., Shacham, S., and London, C.A. (2014). Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines. BMC Vet. Res., 10.","DOI":"10.1186\/1746-6148-10-160"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gao, Y., Packeiser, E.M., Wendt, S., Sekora, A., Cavalleri, J.M.V., Pratscher, B., Alammar, M., H\u00fchns, M., Brenig, B., and Junghanss, C. (2024). Cross-Species Comparison of the Pan-RAF Inhibitor LY3009120\u2019s Anti-Tumor Effects in Equine, Canine, and Human Malignant Melanoma Cell Lines. Genes, 15.","DOI":"10.3390\/genes15020202"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.vetimm.2015.11.003","article-title":"Cancer immunology and canine malignant melanoma: A comparative review","volume":"169","author":"Atherton","year":"2016","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/nbt1137","article-title":"Monoclonal antibody therapy of cancer","volume":"23","author":"Adams","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/00002371-199410000-00003","article-title":"Potential to involve multiple effector cells with human recombinant interleukin-2 and antiganglioside monoclonal antibodies in a canine malignant melanoma immunotherapy model","volume":"16","author":"Helfand","year":"1994","journal-title":"J. Immunother. Emphas. Tumor. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1001\/jama.1994.03510360033032","article-title":"Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2","volume":"271","author":"Rosenberg","year":"1994","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Alsaab, H.O., Sau, S., Alzhrani, R., Tatiparti, K., Bhise, K., Kashaw, S.K., and Iyer, A.K. (2017). PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00561"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lee, H.T., Lee, J.Y., Lim, H., Lee, S.H., Moon, Y.J., Pyo, H.J., Ryu, S.E., Shin, W., and Heo, Y.S. (2017). Molecular mechanism of PD-1\/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06002-8"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Maekawa, N., Konnai, S., Takagi, S., Kagawa, Y., Okagawa, T., Nishimori, A., Ikebuchi, R., Izumi, Y., Deguchi, T., and Nakajima, C. (2017). A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09444-2"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Igase, M., Nemoto, Y., Itamoto, K., Tani, K., Nakaichi, M., Sakurai, M., Sakai, Y., Noguchi, S., Kato, M., and Tsukui, T. (2020). A pilot clinical study of the therapeutic antibody against canine PD-1 for advanced spontaneous cancers in dogs. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-75533-4"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kamoto, S., Shinada, M., Kato, D., Yoshimoto, S., Ikeda, N., Tsuboi, M., Yoshitake, R., Eto, S., Hashimoto, Y., and Takahashi, Y. (2020). Phase I\/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma. Cells, 9.","DOI":"10.3390\/cells9112529"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chen, S., Zhang, Z., Zheng, X., Tao, H., Zhang, S., Ma, J., Liu, Z., Wang, J., Qian, Y., and Cui, P. (2021). Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.562315"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12943-023-01723-z","article-title":"CAR-cell therapy in the era of solid tumor treatment: Current challenges and emerging therapeutic advances","volume":"22","author":"Maalej","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.apsb.2020.10.020","article-title":"CAR-T cells: Early successes in blood cancer and challenges in solid tumors","volume":"11","author":"Dana","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Forsberg, E.M.V., Riise, R., Saellstr\u00f6m, S., Karlsson, J., Als\u00e9n, S., Bucher, V., Hemminki, A.E., Bagge, R.O., Ny, L., and Nilsson, L.M. (2023). Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs. Cancers, 15.","DOI":"10.3390\/cancers15030648"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/vco.12044","article-title":"Comparative analysis of MAPK and PI3K\/AKT pathway activation and inhibition in human and canine melanoma: Pathway activation and inhibition in human and canine melanoma","volume":"13","author":"Fowles","year":"2015","journal-title":"Vet. Comp. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1111\/j.1365-2133.2007.07821.x","article-title":"Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment","volume":"156","author":"Meier","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/mc.20628","article-title":"Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways","volume":"49","author":"Chen","year":"2010","journal-title":"Mol. Carcinog."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-3-319-91442-8_7","article-title":"Trametinib (GSK1120212)","volume":"211","author":"Zeiser","year":"2018","journal-title":"Recent Results Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1158\/1535-7163.MCT-19-0858","article-title":"Efficacy, Tolerability, and Pharmacokinetics of Combined Targeted MEK and Dual mTORC1\/2 Inhibition in a Preclinical Model of Mucosal Melanoma","volume":"19","author":"Wei","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00280-023-04534-7","article-title":"Comparative biochemical kinase activity analysis identifies rivoceranib as a highly selective VEGFR2 inhibitor","volume":"91","author":"Jang","year":"2023","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Li, Q., Kim, Y.-S., An, J.-H., Kwon, J.-A., Han, S.-H., Song, W.-J., and Youn, H.-Y. (2021). Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-021-03026-1"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tani, H., Miyamoto, R., Noguchi, S., Kurita, S., Nagashima, T., Michishita, M., Yayoshi, N., Tamura, K., and Bonkobara, M. (2021). A canine case of malignant melanoma carrying a KIT c.1725_1733del mutation treated with toceranib: A case report and in vitro analysis. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-021-02864-3"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Brocca, G., Poncina, B., Sammarco, A., Cavicchioli, L., and Castagnaro, M. (2020). KIT Somatic Mutations and Immunohistochemical Expression in Canine Oral Melanoma. Animals, 10.","DOI":"10.3390\/ani10122370"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/vco.12546","article-title":"Pevonedistat targeted therapy inhibits canine melanoma cell growth through induction of DNA re-replication and senescence","volume":"18","author":"Wood","year":"2020","journal-title":"Vet. Comp. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bernard, S., Poon, A.C., Tam, P.M., and Mutsaers, A.J. (2021). Investigation of the effects of mTOR inhibitors rapamycin and everolimus in combination with carboplatin on canine malignant melanoma cells. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-021-03089-0"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Youssef, M.E., Cavalu, S., Hasan, A.M., Yahya, G., Abd-Eldayem, M.A., and Saber, S. (2023). Role of Ganetespib, an HSP90 Inhibitor, in Cancer Therapy: From Molecular Mechanisms to Clinical Practice. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24055014"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"London, C.A., Bear, M.D., McCleese, J., Foley, K.P., Paalangara, R., Inoue, T., Ying, W., and Barsoum, J. (2011). Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027018"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/vco.12691","article-title":"JARID1-targeted histone H3 demethylase inhibitors exhibit anti-proliferative activity and overcome cisplatin resistance in canine oral melanoma cell lines","volume":"19","author":"Tobin","year":"2021","journal-title":"Vet. Comp. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41392-023-01341-7","article-title":"Targeting epigenetic regulators to overcome drug resistance in cancers","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bbrc.2013.08.020","article-title":"A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model","volume":"439","author":"Fukumoto","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"670451","DOI":"10.3389\/fvets.2021.670451","article-title":"Effects of Alpha-Connexin Carboxyl-Terminal Peptide (aCT1) and Bowman-Birk Protease Inhibitor (BBI) on Canine Oral Mucosal Melanoma (OMM) Cells","volume":"8","author":"Sato","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.biocel.2004.06.005","article-title":"Membrane type-1 matrix metalloproteinase (MT1-MMP) protects malignant cells from tumoricidal activity of re-engineered anthrax lethal toxin","volume":"37","author":"Rozanov","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Nishiya, A.T., Massoco, C.O., Felizzola, C.R., Perlmann, E., Batschinski, K., Tedardi, M.V., Garcia, J.S., Mendon\u00e7a, P.P., Teixeira, T.F., and Dagli, M.L.Z. (2016). Comparative Aspects of Canine Melanoma. Vet. Sci., 3.","DOI":"10.3390\/vetsci3010007"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1158\/0008-5472.CAN-17-3754","article-title":"Remission of Spontaneous Canine Tumors after Systemic Cellular Viroimmunotherapy","volume":"78","author":"Cejalvo","year":"2018","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/mt.2014.7","article-title":"A pRb-responsive, RGD-modified, and Hyaluronidase-armed Canine Oncolytic Adenovirus for Application in Veterinary Oncology","volume":"22","author":"Laborda","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bunnell, B.A. (2021). Adipose Tissue-Derived Mesenchymal Stem Cells. Cells, 10.","DOI":"10.3390\/cells10123433"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ahn, J.O., Lee, H.W., Seo, K.W., Kang, S.K., Ra, J.C., and Youn, H.Y. (2013). Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-\u03b2 and treatment with cisplatin in a xenograft mouse model for canine melanoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074897"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1017\/erm.2023.7","article-title":"MicroRNAs in cancer metastasis: Biological and therapeutic implications","volume":"25","author":"Sell","year":"2023","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/vco.12485","article-title":"Synthetic microRNA-205 exhibited tumour suppression in spontaneous canine malignant melanoma by intratumoral injection","volume":"17","author":"Yoshikawa","year":"2019","journal-title":"Vet. Comp. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1038\/s41417-023-00656-5","article-title":"Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors","volume":"30","author":"Yoshikawa","year":"2023","journal-title":"Cancer Gene Ther."},{"key":"ref_64","first-page":"151","article-title":"MicroRNA-205 enhances the radiosensitivity of canine oral melanoma cells by inhibiting E2F1","volume":"67","author":"Wada","year":"2019","journal-title":"Jpn. J. Vet. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.phrs.2014.03.002","article-title":"The pharmacology of statins","volume":"88","author":"Sirtori","year":"2014","journal-title":"Pharmacol. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s13046-021-02041-2","article-title":"Statins: A repurposed drug to fight cancer","volume":"40","author":"Jiang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Nishiya, A.T., Nagamine, M.K., da Fonseca, I.I.M., Miraldo, A.C., Scattone, N.V., Guerra, J.L., Xavier, J.G., Santos, M., Gomes, C.O.M.d.S., and Ward, J.M. (2020). Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas. Toxins, 12.","DOI":"10.3390\/toxins12030157"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1177\/03009858211011939","article-title":"PD-1, PD-L1, and PD-L2 Gene Expression and Tumor Infiltrating Lymphocytes in Canine Melanoma","volume":"58","author":"Stevenson","year":"2021","journal-title":"Vet. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/annonc\/mdy495","article-title":"Development of tumor mutation burden as an immunotherapy biomarker: Utility for the oncology clinic","volume":"30","author":"Chan","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.1038\/s41467-021-24836-9","article-title":"Canine tumor mutational burden is correlated with TP53 mutation across tumor types and breeds","volume":"12","author":"Alsaihati","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1292\/jvms.21-0646","article-title":"Expression of L-type amino acid transporter 1 in canine and feline intracranial tumors","volume":"84","author":"Utsugi","year":"2022","journal-title":"J. Vet. Med. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lisjak, A., Lopes, B.C., Pilla, R., Nemec, A., Suchodolski, J.S., and Tozon, N. (2023). A Comparison of the Oral Microbiota in Healthy Dogs and Dogs with Oral Tumors. Animals, 13.","DOI":"10.3390\/ani13233594"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kleber, K.T., Iranpur, K.R., Perry, L.M., Cruz, S.M., Razmara, A.M., Culp, W.T.N., Kent, M.S., Eisen, J.A., Rebhun, R.B., and Canter, R.J. (2022). Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.983344"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10387\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:04:23Z","timestamp":1760112263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":73,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910387"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910387","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,26]]}}}