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Liposomal Lapatinib in Combination with Low-Dose Photodynamic Therapy for the Treatment of Glioma.
Fisher, Carl; Obaid, Girgis; Niu, Carolyn; Foltz, Warren; Goldstein, Alyssa; Hasan, Tayyaba; Lilge, Lothar.
Afiliación
  • Fisher C; Department of Molecular Imaging, Princess Margaret Cancer Centre, Toronto, ON M5G1L7, Canada.
  • Obaid G; Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Niu C; Department of Molecular Imaging, Princess Margaret Cancer Centre, Toronto, ON M5G1L7, Canada.
  • Foltz W; Department of Radiation Oncology, University Health Network, Toronto, ON M5G1L7, Canada.
  • Goldstein A; Animal Resources Centre, University Health Network; Toronto, ON M5G1L7, Canada.
  • Hasan T; Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Lilge L; Department of Molecular Imaging, Princess Margaret Cancer Centre, Toronto, ON M5G1L7, Canada.
J Clin Med ; 8(12)2019 Dec 14.
Article en En | MEDLINE | ID: mdl-31847378
BACKGROUND: Malignant gliomas are highly invasive and extremely difficult to treat tumours with poor prognosis and outcomes. Photodynamic therapy (PDT), mediated by Gleolan®, has been studied previously with partial success in treating these tumours and extending lifetime. We aim to determine whether combining PDT using ALA-protoporphyrin IX (PpIX) with a liposomal formulation of the clinical epidermal growth factor receptor (EGFR) inhibitor, lapatinib, would increase the anti-tumour PDT efficacy. METHODS: Lapatinib was given in vitro and in vivo 24 h prior to PDT and for 3-5 days following PDT to elicit whether the combination provided any benefits to PDT therapy. Live-cell imaging, in vitro PDT, and in vivo studies were performed to elucidate the effect lapatinib had on PDT for a variety of glioma cell lines and as well as GSC-30 neurospheres in vivo. RESULTS: PDT combined with lapatinib led to a significant increase in PpIX accumulation, and reductions in the LD50 of PpIX mediated PDT in two EGFR-driven cell lines, U87 and U87vIII, tested (p < 0.05). PDT + lapatinib elicited stronger MRI-quantified glioma responses following PDT for two human glioma-derived tumours (U87 and GSC-30) in vivo (p < 0.05). Furthermore, PDT leads to enhanced survival in rats following treatment with lapatinib compared to lapatinib alone and PDT alone (p < 0.05). CONCLUSIONS: As lapatinib is approved for other oncological indications, a realization of its potential combination with PDT and in fluorescence-guided resection could be readily tested clinically. Furthermore, as its use would only be in acute settings, long-term resistance should not pose an issue as compared to its use as monotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Clin Med Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Clin Med Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza