Lemur tail kinase 3 serves as a predictor of patient outcomes and a target for the treatment of ovarian cancer

Abstract

Lemur tail kinase 3 (LMTK3) belongs to a family of tyrosine kinases that are known to correlate with tumor grade and patient survival in some cancers. Here, we validated LMTK3 as a specific target and a prognostic biomarker in ovarian cancer (OC). In samples from 204 stage I–II OC patients, immunohistochemical studies revealed a higher cytoplasmic-to-nuclear staining intensity of LMTK3, which correlated with worse overall survival (p < 0.001). Efficacy studies utilizing novel LMTK3 binding peptides (LMTK3BPs) showed that all chemosensitive and chemoresistant OC cells were killed without affecting normal cells (p < 0.005), with synergistic effects shown following cisplatin and docetaxel treatment. In an orthotopic xenograft mouse model of OC, we saw a 35% tumor reduction in response to intravenous injections of 2 mg/kg LMTK3BP given three times a week for 3 weeks. Furthermore, in vivo safety studies showed no signs of toxicity after LMTK3BP treatment, even at doses as high as 40 mg/kg. This study highlights LMTK3 as a predictor of patient clinical outcomes. More importantly, novel LMTK3BPs represent potential safe treatment options, either alone or in combination with therapies, for OC.

Keywords

• binding peptides
• chemoresistance
• lemur tail kinase 3
• ovarian cancer
• targeted therapy