Katt William P, Balkman Cheryl E, Butler Scott D, Byron Michael, Carney Patrick C, Todd-Donato Amy B, Drozd Matthew E, Duhamel Gerald E, Evans Jacquelyn M, Fiani Nadine, Ford Jordan C, Grenier Jennifer K, Hayward Jessica J, Heikinheimo Kristiina, Hume Kelly R, Moore Elizabeth S, Puri Rishi, Sylvester Skylar R, Warshaw Sydney L, Webb Suzin M, White Andrew C, Wright Alexandra L, Cerione Richard A, Peralta Santiago
Department of Molecular Medicine, Cornell University, Ithaca, NY, USA.
Department of Clinical Sciences, Cornell University, Ithaca, NY, USA.
Sci Rep. 2025 Feb 27;15(1):7069. doi: 10.1038/s41598-025-90574-3.
Oral tumors are relatively common in dogs, and canine oral squamous cell carcinoma (COSCC) is the most prevalent oral malignancy of epithelial origin. COSCC is locally aggressive with up to 20% of patients showing regional or distant metastasis at the time of diagnosis. The treatment of choice most typically involves wide surgical excision. Although long-term remission is possible, treatments are associated with considerable morbidity and can negatively impact functionality and quality of life. OSCCs have substantial upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously hypothesized that small-molecule inhibitors that target RAS signaling might effectively inhibit tumor growth and progression. Here, we demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for human cancers, substantially inhibits the growth of six COSCC cell lines established from current patient tumor samples. We further show preliminary clinical evidence that the drug is able to cause ~ 40% and ~ 80% tumor regression in two out of four patients with spontaneously occurring COSCC, a partial response according to commonly used RECIST criteria. Given the limited treatment options available and the number of dogs for which standard of care is not acceptable, these preliminary findings provide new hope that more suitable treatment options may soon enter the veterinary clinic.
口腔肿瘤在犬类中相对常见，犬口腔鳞状细胞癌（COSCC）是最常见的上皮源性口腔恶性肿瘤。COSCC具有局部侵袭性，高达20%的患者在诊断时出现区域或远处转移。最典型的治疗选择通常包括广泛的手术切除。虽然长期缓解是可能的，但治疗会带来相当大的发病率，并可能对功能和生活质量产生负面影响。口腔鳞状细胞癌（OSCC）中RAS-RAF-MEK-MAPK信号轴有大量上调，我们之前曾假设靶向RAS信号的小分子抑制剂可能有效抑制肿瘤生长和进展。在此，我们证明MEK抑制剂曲美替尼（一种已获美国食品药品监督管理局批准用于人类癌症的药物）能显著抑制从当前患者肿瘤样本中建立的六种COSCC细胞系的生长。我们进一步展示了初步的临床证据，该药物能够使四例自发发生COSCC的患者中的两例肿瘤消退约40%和约80%，根据常用的RECIST标准这属于部分缓解。鉴于可用的治疗选择有限，以及许多犬只无法接受标准治疗，这些初步发现为更合适的治疗选择可能很快进入兽医临床提供了新希望。
