Establishment of aBRAF V595E‐mutant canine prostate cancer cell line and the antitumor effects ofMEKinhibitors against canine prostate cancer

• DOI: 10.1111/vco.12879
• Publication Date: 2023-02-06T15:18:36Z
• Authors: Masanori Kobayashi; Moe Onozawa; Shiho Watanabe; Tomokazu Nagashima; Kyoichi Tamura; Yoshiaki Kubo; Akiko Ikeda; Kazuhiko Ochiai; Masaki Michishita; Makoto Bonkobara; Masato Kobayashi; Tatsuya Hori; Eiichi Kawakami
• Keywords: Trametinib; V600E

Abstract Canine prostate cancer (cPCa) is a malignant neoplasm with no effective therapy. The BRAF V595E mutation, corresponding to the human V600E found frequently in cPCa. Activating mutations are recognized as oncogenic drivers, and blockade of MAPK/ERK phosphorylation may be an therapeutic target against BRAF‐mutated tumours. aim this study was establish novel cPCa cell line clarify antitumor effects MEK inhibitors on vitro vivo. We established CHP‐2 that derived from prostatic tissue patient. Sequencing canine gene two lines revealed presence mutation. (trametinib, cobimetinib mirdametinib) strongly suppressed proliferation vitro, trametinib showed highest efficacy cells minimal cytotoxicity non‐cancer COPK cells. Furthermore, we orally administered 0.3 or 1.0 mg/kg xenografted mice examined its Trametinib reduced tumour volume, decreased phosphorylated ERK levels, lowered Ki‐67 expression xenografts dose‐dependent manner. Although clear adverse events were observed administration, trametinib‐treated osteogenesis independent dosage. Our results indicate induces cycle arrest by inhibiting activation, resulting regression inhibitors, addition targeted agent option for