Molecular Therapy: Oncology (Sep 2024)

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

  • Ghassan M. Saed,
  • Nicole M. Fletcher,
  • Harvey Sharma,
  • Axel Stenmark Tullberg,
  • Ella Ittner,
  • Toshima Z. Parris,
  • Daniella Pettersson,
  • Anikó Kovács,
  • Elisabeth Werner Rönnerman,
  • Pernilla Dahm-Kähler,
  • Anna Portela,
  • Pamela D. Garzone,
  • Robert Morris,
  • Khalil Helou

Journal volume & issue
Vol. 32, no. 3
p. 200864

Abstract

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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.

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