{"id":1382,"date":"2018-03-27T08:33:25","date_gmt":"2018-03-27T08:33:25","guid":{"rendered":"https:\/\/galenicamed.com\/2018\/03\/27\/canine-oral-malignant-melanoma\/"},"modified":"2018-03-27T08:33:25","modified_gmt":"2018-03-27T08:33:25","slug":"canine-oral-malignant-melanoma","status":"publish","type":"post","link":"https:\/\/galenicamed.com\/es\/2018\/03\/27\/canine-oral-malignant-melanoma\/","title":{"rendered":"Canine oral malignant melanoma"},"content":{"rendered":"

Canine oral malignant melanoma \u2013 new and improved treatments orientating on human melanoma drugs<\/strong><\/p>\n

Animals, and especially dogs are an important companion in people`s lives. In the United States,
\nmore than 70 million homes have at least one pet as the member of the household. Approximately
\n61 million dogs are pets in the USA. Dogs have a significant place in their owners` hearts and lives.
\nPeople with dogs often evaluate their dog-human relationship as more reliable and consistent
\nthan a human-human one (1).
\nThis important bond makes dog owners invest a lot in their dogs\u2019 well-being and health. A lot of
\nresearch is ongoing in order to make the pets\u2019 lives more comfortable and to cure pets\u2019 diseases.
\nConsequently similar to our aging society, dogs live longer than before and an increasing number
\nof them develop and die from cancer nowadays (1).<\/p>\n

\"\"<\/p>\n

Cancer of the oral cavity, such as oral melanoma accounts to around 6% of canine malignancies
\nand is the 4th most common cancer in dogs. Male dogs are more affected, especially cocker
\nspaniel, German shepherd, German shorthaired pointer, Weimaraner, golden retriever, Gordon
\nsetter, miniature poodle, chow chow and boxer. Oral melanoma in dogs appears around 11 years
\nof age and is often very aggressive with very large tumors that commonly invade the surrounding
\nbones of the oral cavity before they are even diagnosed. Oral melanoma is able to metastasize to
\nthe surrounding lymph nodes of the head and neck as well as to the lungs. How can this aggressive
\ncancer type be fought? (2)<\/p>\n

Up to now, the treatment options for oral malignant melanoma (OMM) are very limited. The
\nprimary choice of treatment is surgery but if the tumor has invaded the boney structures of the
\njaw, the complete removal of the tumor tissue is often not possible. In this case, dogs are treated
\nwith radiation therapy and some studies have shown a remission rate of 70% with radiation
\ntherapy only. Adding chemotherapy to the treatment generally does not improve the survival
\ntimes. Besides, dogs treated with carboplatin and dacarbazine are observed with side effects such
\nas vomiting, diarrhea and myelosuppression. All in all, the treatment of oral melanoma is
\nchallenging and survival times even with therapy are often only in the range of 5 to 7 months. This
\npoor survival rate arise the question of if there are any studies on new and more effective
\ntreatment options? (3)<\/p>\n

A few molecular-targeted therapies including tyrosine kinase inhibitors are tested for treatment of
\na limited number of cancer types such as mast cell tumors. Several studies are ongoing to identify
\nnew options for dog cancer treatment and some targeted antibodies have been developed and
\ntested in vitro and in vivo.<\/p>\n

A clinical study conducted by D. A. Grosenbaugh and his colleagues evaluated the safety and
\nefficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment
\nfollowing surgery of the primary tumor. The study was a multicenter clinical trial of 111 dogs with
\nstage II or III OMM in which locoregional control was reached. The treatment included an initial
\nseries of 4 injections of huTyr vaccine (102 microg of DNA \/ injection) which was given to 58 dogs
\ntransdermally with a needle-free IM vaccination device. During the treatment, the appearance of
\nadverse events was monitored. Booster injections at 6-months intervals were given to the
\nsurviving dogs. The results showed that the survival time of OMM was significantly improved for
\ndogs receiving the huTyr vaccine compared to historical controls. The determination of the median
\nsurvival time however was not possible due to < 50% of OMM deaths before the end of the\nobservation period was reached. The vaccination treatment did not cause any systemic reactions\nthat would require veterinary interventions. The only reactions to treatment observed were locally\nand included wheal or hematoma formation as well as mild signs of pain at the injection site. In\nsummary, this study could show that the huTyr vaccine has a good safety and efficacy profile and\ncan serve as adjunctive treatment and improve the treatment results for OMM (4).\n\nSimilar as immunotherapies gained more and more attention in human cancer treatment, they\nalso represent a treatment option to be evaluated for dog cancers.\nA recent study conducted by N. Maekawa and his colleagues determined the antitumor effect of\nc4G12, a canine-chimerised anti-PD-L1 monoclonal antibody in vitro and in a pilot clinical study.\nPD-1 is a receptor that is expressed mainly on activated T-cells and suppresses its activation by\nbinding to the ligands PD-L1 and PD-L2. In humans, tumor antigen-specific T-cells have an\nupregulated PD-1 expression and various cancer types showed an aberrant expression of PD-L1 in\ntheir tumor cells or other cells in the tumor microenvironment. Anti-PD1 or PD-L1 antibodies are\nable to block the PD-1\/PD-L1 pathway and can restore multiple effector functions of antigenspecific\nT cells. In this way, the treatment is thought to reverse the immune evasion mechanisms\nof the cancer cells. PD-L1 is also observed to be expressed in various canine cancer types such as\nOMM, hemangiosarcoma and osteosarcoma. In this study, c4G12 was selected as the therapeutic\ncandidate and its function was tested in vitro and in a clinical study. In vitro, the antibody could\nsignificantly block the binding of recombinant cPD-L1 to both cPD-1 and cCD80. C4G12 appeared\nalso to restore the effector functions of dog lymphocytes which are suppressed by the PD-1\/PD-L1\npathway. The candidate antibody was also tested in a pilot clinical study with seven dogs suffering\nfrom OMM (1 with stage II, 2 with stage III, 4 with stage IV and two dogs with undifferentiated\nsarcoma which had an elevated PD-L1 expression in their tumor tissue. The dogs received 2 or 5\nmg\/kg c4G12 iv every 2 weeks. The results showed that one dog with stage II OMM had an\nobvious tumor regression after 10 weeks of treatment. In the other 6 dogs with OMM, no tumor\nregression was observed. The objective response rate was 14.3%. There were no treatmentrelated\nadverse events observed. The survival in dogs with OMM compared to a control group was\n93.5 days and 54 days, respectively (p = 0.1). In summary, this study could demonstrate the safety\nand anti-tumor activity of anti-PD-L1 mAb in dogs (5).\n\nFurther studies are needed to establish a dog cancer treatment. These kind of studies can also\nserve to inform human preclinical studies PD-1\/PD-L1 inhibiting-mAbs.\n\n\nReferences: \n1. \tM. J. Dotson, E. M. Hyatt, Understanding dog-human companionship. Journal of business research, 61, 457-66, 2008.\n2. \tD. E. Bostock, Prognosis after surgical excision of canine melanomas. Vet Pathol, 16, 32-40, 1979.\n3. \tH.J. Harvey, E. G. MacEwen, D. Braun et al. Prognostic criteria for dogs with oral melanoma. J Am Vet Med Assoc, 178, 580-2, 1981.\n4. \tD. A. Grosenbaugh, A. T. Leard, P. J. Bergman, M. K. Klein, K. Meleo, S. Susaneck, P. R. Hess, M. K. Jankowski, P. D. Jones, N. F. Leibman, M. H. Johnson, I. D. Kurzman, J. D. Wolchok. Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor. AJVR, 72, 12, Dec, 2011.\n5. \tN. Maekawa, S. Konnai, S. Takagi, Y. Kagawa, T. Okawaga, A. Nishimori, R. Ikebuchi, Y. Izumi, T. Deguchi, C. Nakajima, Y. Kato, K. Yamamoto, H. Uemura, Y. Suzuki, S. Murata, K. Ohashi. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma of undifferentiated sarcoma. Scientific reports, 7:8951, Aug, 2017.\n\n<\/p>\n","protected":false},"excerpt":{"rendered":"

Canine oral malignant melanoma \u2013 new and improved treatments orientating on human melanoma drugs Animals, and especially dogs are an important companion in people`s lives. In the United States, more than 70 million homes have at least one pet as the member of the household….<\/p>\n","protected":false},"author":1,"featured_media":1293,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[101],"tags":[],"_links":{"self":[{"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/posts\/1382"}],"collection":[{"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/comments?post=1382"}],"version-history":[{"count":0,"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/posts\/1382\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/media\/1293"}],"wp:attachment":[{"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/media?parent=1382"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/categories?post=1382"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/galenicamed.com\/es\/wp-json\/wp\/v2\/tags?post=1382"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}