A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.

Autoren

Richard E Kast
John A Boockvar
Ansgar Brüning
Francesco Cappello
Wen-Wei Chang
Boris Cvek
Q Ping Dou
Alfonso Duenas-Gonzalez
Thomas Efferth
Daniele Focosi
Seyed H Ghaffari
Georg Karpel-Massler
Kirsi Ketola
Alireza Khoshnevisan
Daniel Keizman
Nicolas Magné
Christine Marosi
Kerrie McDonald
Miguel Muñoz
Ameya Paranjpe
Mohammad H Pourgholami
Iacopo Sardi
Avishay Sella
Kalkunte S Srivenugopal
Marco Tuccori
Weiguang Wang
Christian R Wirtz
Marc-Eric Halatsch

DOI

10.18632/oncotarget.969

eISSN

1949-2553

Ausgabe der Veröffentlichung

4

Zeitschrift

Oncotarget

Sprache

en

Online publication date

2013

Paginierung

502 - 530

Datum der Veröffentlichung

2013

Status

Published

Herausgeber

Impact Journals, LLC

Herausgeber URL

http://dx.doi.org/10.18632/oncotarget.969

Datum der Datenerfassung

2023

Titel

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Ausgabe der Zeitschrift

4

Data source: Crossref

Abstract

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

Addresses

IIAIGC Headquarters, Dean of Studies, Burlington, VT, USA. richarderickast@gmail.com

Autoren

Richard E Kast
John A Boockvar
Ansgar Brüning
Francesco Cappello
Wen-Wei Chang
Boris Cvek
Q Ping Dou
Alfonso Duenas-Gonzalez
Thomas Efferth
Thomas Efferth
Daniele Focosi
Seyed H Ghaffari
Georg Karpel-Massler
Kirsi Ketola
Alireza Khoshnevisan
Daniel Keizman
Nicolas Magné
Christine Marosi
Kerrie McDonald
Miguel Muñoz
Ameya Paranjpe
Mohammad H Pourgholami
Iacopo Sardi
Avishay Sella
Kalkunte S Srivenugopal
Marco Tuccori
Weiguang Wang
Christian R Wirtz
Marc-Eric Halatsch

DOI

10.18632/oncotarget.969

eISSN

1949-2553

Externe Identifier

PubMed Identifier: 23594434
PubMed Central ID: PMC3720600

Open access

true

ISSN

1949-2553

Ausgabe der Veröffentlichung

4

Zeitschrift

Oncotarget

Schlüsselwörter

Humans
Glioblastoma
Brain Neoplasms
Neoplasm Recurrence, Local
Sertraline
Disulfiram
Succinates
Gluconates
Artemisinins
Auranofin
Dacarbazine
Morpholines
Ketoconazole
Nelfinavir
Captopril
Antineoplastic Combined Chemotherapy Protocols
Temozolomide
Aprepitant

Sprache

eng

Medium

Print

Open access status

Open Access

Paginierung

502 - 530

Datum der Veröffentlichung

2013

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2013

Titel

A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.

Sub types

review-article
Review
Journal Article

Ausgabe der Zeitschrift

4

Files

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=969&path%5B%5D=1281 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23594434/pdf/?tool=EBI https://europepmc.org/articles/PMC3720600?pdf=render

Data source: Europe PubMed Central

Abstract

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

Autoren

Richard E Kast
John A Boockvar
Ansgar Brüning
Francesco Cappello
Wen-Wei Chang
Boris Cvek
Q Ping Dou
Alfonso Duenas-Gonzalez
Thomas Efferth
Daniele Focosi
Seyed H Ghaffari
Georg Karpel-Massler
Kirsi Ketola
Alireza Khoshnevisan
Daniel Keizman
Nicolas Magné
Christine Marosi
Kerrie McDonald
Miguel Muñoz
Ameya Paranjpe
Mohammad H Pourgholami
Iacopo Sardi
Avishay Sella
Kalkunte S Srivenugopal
Marco Tuccori
Weiguang Wang
Christian R Wirtz
Marc-Eric Halatsch

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/23594434

DOI

10.18632/oncotarget.969

eISSN

1949-2553

Externe Identifier

PubMed Central ID: PMC3720600

Ausgabe der Veröffentlichung

4

Zeitschrift

Oncotarget

Schlüsselwörter

Antineoplastic Combined Chemotherapy Protocols
Aprepitant
Artemisinins
Auranofin
Brain Neoplasms
Captopril
Dacarbazine
Disulfiram
Glioblastoma
Gluconates
Humans
Ketoconazole
Morpholines
Nelfinavir
Neoplasm Recurrence, Local
Sertraline
Succinates
Temozolomide

Sprache

eng

Country

United States

Paginierung

502 - 530

PII

969

Datum der Veröffentlichung

2013

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2013

Titel

A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.

Sub types

Journal Article
Review

Ausgabe der Zeitschrift

4

Data source: PubMed

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.

Files

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