Frontiers in Oncology (Oct 2023)

Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report

  • Michael P. Castro,
  • Michael P. Castro,
  • Michael P. Castro,
  • Bence Sipos,
  • Saskia Biskup,
  • Nina Kahn

DOI
https://doi.org/10.3389/fonc.2023.1210224
Journal volume & issue
Vol. 13

Abstract

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Network targeting of disease-specific nodes represents a useful principle for designing combination cancer therapy. In this case of a patient with relapsed leptomeningeal glioblastoma, comprehensive molecular diagnosis led to the identification of a disease network characterized by multiple disease-specific synthetic lethal vulnerabilities involving DNA repair, REDOX homeostasis, and impaired autophagy which suggested a novel network-targeting combination therapy (NTCT). A treatment regimen consisting of lomustine, olaparib, digoxin, metformin, and high dose intravenous ascorbate was employed using the principle of intra-patient dose escalation to deliver the treatment with adequate safety measures to achieve a definitive clinical result.

Keywords