{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:50:21Z","timestamp":1791298221393,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>A 13-year-old spayed female Shih Tzu presented with a several-month history of progressively increasing liver enzyme activities concurrent with managed hyperadrenocorticism. Diagnostic imaging revealed a solitary hepatic mass originating from the caudate process of the caudate lobe adhering to the caudal vena cava. Hepatocellular carcinoma (HCC) was confirmed via histopathological examination of an ultrasound-guided tru-cut biopsy, accompanied by a markedly elevated serum alpha-fetoprotein (AFP) concentration. Molecular targeted therapy with olaparib was initiated since complete surgical resection was unachievable due to tumor adherence to the caudal vena cava and conventional chemotherapy has limited efficacy for canine HCC, based on genomic profiling. Following objective tumor progression and worsening mass effect after 2\u202fmonths, cytoreductive surgery was performed. Postoperatively, olaparib and canine interleukin-15 (cIL-15) immunotherapy were instituted to control potential micrometastases. The patient achieved clinical and radiographic stability for a 10-month follow-up period, accompanied by a significant drop in serum AFP levels. However, following the discontinuation of cIL-15 and subsequent reduction of olaparib dosage because of suspected adverse effects, serum AFP levels rebounded progressively, and tumor recurrence was confirmed via ultrasonography. The patient died 20\u202fmonths after the initial detection of the mass. This case describes the clinical course of canine HCC managed with a multimodal therapeutic approach and highlights the potential utility of serum AFP as an adjunctive biomarker for disease monitoring.<\/jats:p>","DOI":"10.3389\/fvets.2026.1942682","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:51:40Z","timestamp":1791294700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Long term multimodality treatment of canine hepatocellular carcinoma with serial monitoring of serum alpha-fetoprotein"],"prefix":"10.3389","volume":"13","author":[{"given":"Tae-Jung","family":"Dan","sequence":"first","affiliation":[{"name":"Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol-Ho","family":"Yang","sequence":"additional","affiliation":[{"name":"Times Animal Medical Center","place":["Suwon-si, Gyeonggi-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Bio-animal Health, Jangan University","place":["Hwaseong, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Ae","family":"Kang","sequence":"additional","affiliation":[{"name":"VET and GENE","place":["Seongnam, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Sup","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Myung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref1","first-page":"1852","volume-title":"Textbook of Veterinary Internal Medicine","author":"Nick","year":"2024"},{"key":"ref2","first-page":"229","volume-title":"BSAVA Manual of Canine and Feline Oncology","author":"Jonathan","year":"2016"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1080\/00480169.2017.1319304","article-title":"Impact of surgical margins on survival of 37 dogs with massive hepatocellular carcinoma","volume":"65","author":"Matsuyama","year":"2017","journal-title":"N Z Vet J"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.cca.2016.10.006","article-title":"Alpha-foetoprotein (AFP): a multi-purpose marker in hepatocellular carcinoma","volume":"463","author":"Sauzay","year":"2016","journal-title":"Clin Chim Acta"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1177\/104063870601800312","article-title":"Alpha-fetoprotein in serum and tumor tissues in dogs with hepatocellular carcinoma","volume":"18","author":"Kitao","year":"2006","journal-title":"J Vet Diagn Invest"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1292\/jvms.61.657","article-title":"Serum alpha-fetoprotein values in dogs with various hepatic diseases","volume":"61","author":"Yamada","year":"1999","journal-title":"J Vet Med Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1007\/s00280-015-2861-1","article-title":"Targeted therapy in cancer","volume":"76","author":"Tsimberidou","year":"2015","journal-title":"Cancer Chemother Pharmacol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.flm.2017.06.001","article-title":"Molecular targeted therapy of cancer: the progress and future prospect","volume":"1","author":"Ke","year":"2017","journal-title":"Front Lab Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ejphar.2018.07.034","article-title":"Molecular targeted therapy: treating cancer with specificity","volume":"834","author":"Lee","year":"2018","journal-title":"Eur J Pharmacol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e001428","DOI":"10.1136\/jitc-2020-001428","article-title":"Interleukin-15 and cancer: some solved and many unsolved questions","volume":"8","author":"Fiore","year":"2020","journal-title":"J Immunother Cancer"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.cytogfr.2017.08.002","article-title":"Immunobiology of the IL-15\/IL-15R\u03b1 complex as an antitumor and antiviral agent","volume":"38","author":"Guo","year":"2017","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.cytogfr.2016.06.001","article-title":"Interleukin 15: a key cytokine for immunotherapy","volume":"31","author":"Patidar","year":"2016","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.imlet.2017.08.010","article-title":"The potential and promise of IL-15 in immuno-oncogenic therapies","volume":"190","author":"Robinson","year":"2017","journal-title":"Immunol Lett"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1111\/j.1476-5829.2011.00262.x","article-title":"Single-agent gemcitabine chemotherapy in dogs with hepatocellular carcinomas","volume":"9","author":"Elpiner","year":"2011","journal-title":"Vet Comp Oncol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.3390\/cancers12051272","article-title":"Sorafenib for the treatment of unresectable hepatocellular carcinoma: preliminary toxicity and activity data in dogs","volume":"12","author":"Marconato","year":"2020","journal-title":"Cancers"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"35","DOI":"10.5326\/JAAHA-MS-6788","article-title":"Short-term administration of single-agent toceranib in six cases of inoperable massive canine hepatocellular carcinoma","volume":"55","author":"Heishima","year":"2019","journal-title":"J Am Anim Hosp Assoc"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1162665","DOI":"10.3389\/fphar.2023.1162665","article-title":"Olaparib and advanced ovarian cancer: summary of the past and looking into the future","volume":"14","author":"Maiorano","year":"2023","journal-title":"Front Pharmacol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/978-3-319-91442-8_15","volume-title":"Small Molecules in Oncology","author":"Bochum","year":"2018"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1056\/NEJMoa1706450","article-title":"Olaparib for metastatic breast cancer in patients with a germline BRCA mutation","volume":"377","author":"Robson","year":"2017","journal-title":"N Engl J Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/S1470-2045(14)70228-1","article-title":"Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial","volume":"15","author":"Ledermann","year":"2014","journal-title":"Lancet Oncol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"8109","DOI":"10.1158\/0008-5472.CAN-06-0140","article-title":"Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition","volume":"66","author":"McCabe","year":"2006","journal-title":"Cancer Res"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12943-021-01315-9","article-title":"PARP inhibitor olaparib overcomes sorafenib resistance through reshaping the pluripotent transcriptome in hepatocellular carcinoma","volume":"20","author":"Yang","year":"2021","journal-title":"Mol Cancer"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.tibs.2013.05.005","article-title":"Menin: a scaffold protein that controls gene expression and cell signaling","volume":"38","author":"Matkar","year":"2013","journal-title":"Trends Biochem Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1530\/ERC-21-0247","article-title":"Loss of MEN1 function impairs DNA repair capability of pancreatic neuroendocrine tumors","volume":"29","author":"Lakiza","year":"2022","journal-title":"Endocr Relat Cancer"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"155599","DOI":"10.1016\/j.cyto.2021.155599","article-title":"Safety and immunological effects of recombinant canine IL-15 in dogs","volume":"148","author":"Lee","year":"2021","journal-title":"Cytokine"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1596084","DOI":"10.3389\/fvets.2025.1596084","article-title":"Immunotherapeutic efficacy of recombinant canine IL-15 as an adjunct to chemotherapy in canine lymphoma","volume":"12","author":"Kang","year":"2025","journal-title":"Front Vet Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1603421","DOI":"10.3389\/fvets.2025.1603421","article-title":"Safety and efficacy of canine recombinant IL-15 in mammary gland tumors","volume":"12","author":"Kang","year":"2025","journal-title":"Front Vet Sci"},{"key":"ref28","first-page":"117","article-title":"Molecular mechanisms of alpha-fetoprotein gene expression","volume":"65","author":"Lazarevich","year":"2000","journal-title":"Biochemistry (Mosc)"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1111\/liv.14223","article-title":"Biology and significance of alpha-fetoprotein in hepatocellular carcinoma","volume":"39","author":"Galle","year":"2019","journal-title":"Liver Int"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/mc.70092","article-title":"Molecular insights into canine hepatocellular carcinoma: a cross-species transcriptomic comparison with human HCC","volume":"65","author":"Arif","year":"2026","journal-title":"Mol Carcinog"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1942682\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:51:44Z","timestamp":1791294704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1942682\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":30,"alternative-id":["10.3389\/fvets.2026.1942682"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2026.1942682","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"1942682"}}