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

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-...

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Autores principales: Castro, Michael P., Sipos, Bence, Biskup, Saskia, Kahn, Nina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644375/
https://www.ncbi.nlm.nih.gov/pubmed/38023264
http://dx.doi.org/10.3389/fonc.2023.1210224
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author Castro, Michael P.
Sipos, Bence
Biskup, Saskia
Kahn, Nina
author_facet Castro, Michael P.
Sipos, Bence
Biskup, Saskia
Kahn, Nina
author_sort Castro, Michael P.
collection PubMed
description 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.
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spelling pubmed-106443752023-01-01 Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report Castro, Michael P. Sipos, Bence Biskup, Saskia Kahn, Nina Front Oncol Oncology 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. Frontiers Media S.A. 2023-10-31 /pmc/articles/PMC10644375/ /pubmed/38023264 http://dx.doi.org/10.3389/fonc.2023.1210224 Text en Copyright © 2023 Castro, Sipos, Biskup and Kahn https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Castro, Michael P.
Sipos, Bence
Biskup, Saskia
Kahn, Nina
Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report
title Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report
title_full Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report
title_fullStr Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report
title_full_unstemmed Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report
title_short Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report
title_sort network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644375/
https://www.ncbi.nlm.nih.gov/pubmed/38023264
http://dx.doi.org/10.3389/fonc.2023.1210224
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