Details

Autor(en) / Beteiligte

• Paret, Claudia
• Russo, Alexandra
• Otto, Henrike
• Mayer, Arnulf
• Zahnreich, Sebastian
• Wagner, Wolfgang
• Samuel, David
• Scharnhorst, David
• Solomon, David A
• Dhall, Girish
• Wong, Kenneth
• Bender, Hannah
• Alt, Francesca
• Wingerter, Arthur
• Neu, Marie A
• Beck, Olaf
• Prawitt, Dirk
• Eder, Stefan
• Henninger, Nicole
• El Malki, Khalifa
• Lehmann, Nadine
• Backes, Nora
• Roth, Lea
• Seidmann, Larissa
• Sommer, Clemens
• Brockmann, Marc A
• Staatz, Gundula
• Schmidberger, Heinz
• Faber, Jörg

Titel

Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined with radiotherapy

Ist Teil von

• Oncotarget, 2017-12, Vol.8 (69), p.114210-114225

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• High-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a rare, highly malignant tumor. At the time of this publication, no standard protocol exists to treat this tumor entity. In this work, we tested the responsiveness of the primary culture PhKh1 derived from tumor tissue from a pediatric HGNET-BCOR patient (P1) to inhibitors of the Sonic hedgehog pathway combined with radiation. The SMO inhibitors vismodegib and itraconazole had low effect on the proliferation of the PhKh1 cells. However, the GLI inhibitor arsenic trioxide reduced the expression of GLI target genes in the PhKh1 cells and in combination with radiotherapy significantly decreased their clonogenic potential. PhKh1 cells resistant to arsenic trioxide were characterized by the overexpression of molecular chaperones. We combined arsenic trioxide and radiation in the relapse therapy protocol of P1, achieving complete remission after seven weeks. Clinical remission lasted for six months, when P1 developed systemic metastases. Meanwhile, an increase in the concentration of circulating tumor DNA carrying a BCOR internal tandem duplication was observed. Molecular characterization of a second patient (P2) was also performed. In P2, we detected a larger tandem duplication and greater activation of the Sonic hedgehog pathway than in P1. These findings suggest that combining arsenic trioxide with radiotherapy may represent a new therapeutic approach. Moreover, peripheral blood analysis for circulating tumor DNA could help in the early detection of systemic metastases.