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Vincristine resistance in relapsed neuroblastoma can be efficiently overcome by Smac mimetic LCL161 treatment

Kristin Frommann1, Birgit Appl1, Patrick Hundsdoerfer2

  • 1Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.

Journal of Pediatric Surgery
|February 20, 2018
PubMed
Abstract

Insights

Smac mimetics can overcome chemotherapy resistance in neuroblastoma. These drugs target apoptosis regulators, offering new hope for treating relapsed or resistant neuroblastoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Neuroblastomas frequently relapse or metastasize despite initial treatment.
  • Cancer cells often evade apoptosis through elevated anti-apoptotic signals, leading to drug resistance.
  • Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are implicated in cancer progression.

Purpose of the Study:

  • To investigate the role of IAPs in neuroblastoma chemoresistance.
  • To evaluate the efficacy of Smac mimetics in overcoming drug resistance in neuroblastoma models.

Main Methods:

  • Compared IAP expression in paired neuroblastoma cell lines (diagnosis vs. post-chemotherapy).
  • Assessed the effects of vincristine on cell viability, apoptosis, and caspase activation.
  • Determined the impact of Smac mimetic LCL161 on vincristine efficacy in sensitive and resistant cell lines.

Main Results:

  • Increased expression of cIAP-1 and XIAP was observed in the chemoresistant cell line (CHLA-20).
  • Vincristine showed reduced efficacy in the resistant cell line.
  • Smac mimetic LCL161 enhanced vincristine's effects and overcame resistance in CHLA-20 cells.

Conclusions:

  • Elevated IAP levels contribute to vincristine resistance in neuroblastoma.
  • Smac mimetics show promise as a therapeutic strategy to treat relapsed and resistant neuroblastoma.
  • Targeting IAPs with Smac mimetics represents a potential novel approach for neuroblastoma treatment.
Keywords:
ChemoresistanceInhibitor of apoptosis proteinsNeuroblastomaRelapseSmac mimeticsVincristine

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