disulfiram and Benign Neoplasms, Brain studies

Research Excerpts

Excerpt	Relevance	Reference
"Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ)."	9.30	A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma. ( Boockvar, J; Campian, JL; Chaudhary, R; Chinnaiyan, P; Cohen, AL; Fink, K; Goldlust, S; Huang, J; Marcus, S; Wan, L, 2019)
"Disulfiram has shown promising activity including proteasome inhibitory properties and synergy with temozolomide in preclinical glioblastoma (GBM) models."	9.27	Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma. ( Ansstas, G; Campian, JL; DeWees, TA; Gujar, AD; Huang, J; Kim, AH; Lockhart, AC; Tran, DD; Tsien, C, 2018)
" Development strategies using molecular encapsulation of DS and the parenteral dosage forms improve the anticancer pharmacology of the drug."	7.01	Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma - a systematic literature review. ( Benkő, BM; Lamprou, DA; Sebe, I; Sebestyén, A; Zelkó, R, 2023)
"Hypoxia is one of the determinants of GSC."	5.72	PLGA-Nano-Encapsulated Disulfiram Inhibits Hypoxia-Induced NF-κB, Cancer Stem Cells, and Targets Glioblastoma In Vitro and In Vivo. ( Armesilla, AL; Azar, K; Bian, XW; Kannappan, V; Kilari, RS; Kurusamy, S; Liu, P; Liu, Y; Morris, MR; Najlah, M; Wang, W; Wang, Z, 2022)
"Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs)."	5.42	Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors. ( Choi, JW; Choi, SA; Eum, D; Kim, IH; Kim, SK; Lee, JY; Park, KD; Park, SH; Phi, JH; Wang, KC, 2015)
"These brain tumors are often resistant to chemotherapies like temozolomide (TMZ) and there are very few treatment options available to patients."	5.38	Disulfiram, a drug widely used to control alcoholism, suppresses the self-renewal of glioblastoma and over-rides resistance to temozolomide. ( Berns, R; Dunn, SE; Fotovati, A; Hu, K; Kast, RE; Kong, E; Lee, C; Luk, M; Pambid, M; Toyota, B; Toyota, E; Triscott, J; Yip, S, 2012)
"Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ)."	5.30	A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma. ( Boockvar, J; Campian, JL; Chaudhary, R; Chinnaiyan, P; Cohen, AL; Fink, K; Goldlust, S; Huang, J; Marcus, S; Wan, L, 2019)
"Disulfiram has shown promising activity including proteasome inhibitory properties and synergy with temozolomide in preclinical glioblastoma (GBM) models."	5.27	Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma. ( Ansstas, G; Campian, JL; DeWees, TA; Gujar, AD; Huang, J; Kim, AH; Lockhart, AC; Tran, DD; Tsien, C, 2018)
"Constructed from a theoretical framework, the coordinated undermining of survival paths in glioblastoma (GBM) is a combination of nine drugs approved for non-oncological indications (CUSP9; aprepitant, auranofin, captopril, celecoxib, disulfiram, itraconazole, minocycline, quetiapine, and sertraline) combined with temozolomide (TMZ)."	3.91	The efficacy of a coordinated pharmacological blockade in glioblastoma stem cells with nine repurposed drugs using the CUSP9 strategy. ( Grieg, Z; Langmoen, IA; Sandberg, CJ; Skaga, E; Skaga, IØ; Vik-Mo, EO, 2019)
" Development strategies using molecular encapsulation of DS and the parenteral dosage forms improve the anticancer pharmacology of the drug."	3.01	Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma - a systematic literature review. ( Benkő, BM; Lamprou, DA; Sebe, I; Sebestyén, A; Zelkó, R, 2023)
"Among the different types of brain tumors, glioblastoma (GBM) is considered the most aggressive and remains extremely difficult to treat."	2.52	Concise review: bullseye: targeting cancer stem cells to improve the treatment of gliomas by repurposing disulfiram. ( Dunn, SE; Rose Pambid, M; Triscott, J, 2015)
"Hypoxia is one of the determinants of GSC."	1.72	PLGA-Nano-Encapsulated Disulfiram Inhibits Hypoxia-Induced NF-κB, Cancer Stem Cells, and Targets Glioblastoma In Vitro and In Vivo. ( Armesilla, AL; Azar, K; Bian, XW; Kannappan, V; Kilari, RS; Kurusamy, S; Liu, P; Liu, Y; Morris, MR; Najlah, M; Wang, W; Wang, Z, 2022)
"Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs)."	1.42	Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors. ( Choi, JW; Choi, SA; Eum, D; Kim, IH; Kim, SK; Lee, JY; Park, KD; Park, SH; Phi, JH; Wang, KC, 2015)
"These brain tumors are often resistant to chemotherapies like temozolomide (TMZ) and there are very few treatment options available to patients."	1.38	Disulfiram, a drug widely used to control alcoholism, suppresses the self-renewal of glioblastoma and over-rides resistance to temozolomide. ( Berns, R; Dunn, SE; Fotovati, A; Hu, K; Kast, RE; Kong, E; Lee, C; Luk, M; Pambid, M; Toyota, B; Toyota, E; Triscott, J; Yip, S, 2012)

Research

Studies (27)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Median Duration of Overall Survival

Timeframe	Studies, this research(%)	All Research%
pre-1990	1 (3.70)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (7.41)	29.6817
2010's	20 (74.07)	24.3611
2020's	4 (14.81)	2.80

Authors	Studies
Serra, R	1
Zhao, T	1
Huq, S	1
Gorelick, NL	1
Casaos, J	1
Cecia, A	1
Mangraviti, A	1
Eberhart, C	1
Bai, R	1
Olivi, A	1
Brem, H	1
Jackson, EM	1
Tyler, B	1
Kannappan, V	3
Liu, Y	1
Wang, Z	1
Azar, K	1
Kurusamy, S	1
Kilari, RS	1
Armesilla, AL	3
Morris, MR	1
Najlah, M	1
Liu, P	3
Bian, XW	1
Wang, W	7
Benkő, BM	1
Lamprou, DA	1
Sebestyén, A	1
Zelkó, R	1
Sebe, I	1
Jangra, A	1
Choi, SA	3
Yang, J	1
Koh, EJ	1
Phi, JH	3
Lee, JY	3
Wang, KC	3
Kim, SK	4
Lee, YE	1
Kwack, PA	1
Kim, HJ	2
Kim, IH	3
Chong, S	1
Park, SH	2
Park, KD	2
Hwang, DW	1
Joo, KM	1
Huang, J	2
Campian, JL	2
Gujar, AD	1
Tsien, C	1
Ansstas, G	1
Tran, DD	1
DeWees, TA	1
Lockhart, AC	1
Kim, AH	1
Mettang, M	1
Meyer-Pannwitt, V	1
Karpel-Massler, G	3
Zhou, S	1
Carragher, NO	1
Föhr, KJ	1
Baumann, B	1
Nonnenmacher, L	1
Enzenmüller, S	1
Dahlhaus, M	1
Siegelin, MD	1
Stroh, S	1
Mertens, D	1
Fischer-Posovszky, P	1
Schneider, EM	1
Halatsch, ME	4
Debatin, KM	1
Westhoff, MA	1
Koh, HK	1
Seo, SY	1
Kim, JH	1
Chie, EK	1
Chaudhary, R	1
Cohen, AL	1
Fink, K	1
Goldlust, S	1
Boockvar, J	1
Chinnaiyan, P	1
Wan, L	1
Marcus, S	1
Skaga, E	1
Skaga, IØ	1
Grieg, Z	1
Sandberg, CJ	1
Langmoen, IA	1
Vik-Mo, EO	1
Darling, JL	3
Kast, RE	5
Boockvar, JA	1
Brüning, A	1
Cappello, F	1
Chang, WW	1
Cvek, B	2
Dou, QP	1
Duenas-Gonzalez, A	1
Efferth, T	1
Focosi, D	1
Ghaffari, SH	1
Ketola, K	1
Khoshnevisan, A	1
Keizman, D	1
Magné, N	1
Marosi, C	1
McDonald, K	1
Muñoz, M	1
Paranjpe, A	2
Pourgholami, MH	1
Sardi, I	1
Sella, A	1
Srivenugopal, KS	2
Tuccori, M	1
Wirtz, CR	1
Zhang, R	1
Ali-Osman, F	1
Bobustuc, GC	1
Choi, JW	1
Eum, D	1
Zembko, I	1
Ahmed, I	1
Farooq, A	1
Dail, J	1
Tawari, P	2
Mcconville, C	2
Triscott, J	2
Rose Pambid, M	1
Dunn, SE	2
Belda-Iniesta, C	1
Brown, S	2
Goktug, T	1
Channathodiyil, P	2
Hugnot, JP	1
Guichet, PO	1
Bian, X	1
Lee, C	1
Hu, K	1
Fotovati, A	1
Berns, R	1
Pambid, M	1
Luk, M	1
Kong, E	1
Toyota, E	1
Yip, S	1
Toyota, B	1
Hothi, P	1
Martins, TJ	1
Chen, L	1
Deleyrolle, L	1
Yoon, JG	1
Reynolds, B	1
Foltz, G	1
Marikovsky, M	1
Nevo, N	1
Vadai, E	1
Harris-Cerruti, C	1
Goldstein, M	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase II, Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety, Tolerability, and Efficacy of DIsulfiram and Copper Gluconate in Recurrent Glioblastoma[NCT03034135]	Phase 2	23 participants (Actual)	Interventional	2017-03-09	Completed
DIRECT (DIsulfiram REsponse as add-on to ChemoTherapy in Recurrent) Glioblastoma: A Randomized Controlled Trial[NCT02678975]	Phase 2/Phase 3	88 participants (Actual)	Interventional	2017-01-31	Completed
Randomized Phase 2 Trial of Treatment of Advanced Non Small Cell Lung Carcinoma With/Without Disulfiram and Cisplatin Navelbine[NCT00312819]	Phase 2/Phase 3	60 participants (Anticipated)	Interventional	2006-03-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Duration of overall survival for patients that are alive (NCT03034135)
Timeframe: 14 months

Median Progression Free Survival

Intervention	months (Median)
DSF-Cu	7.1

Duration of progression free survival according to RANO criteria (NCT03034135)
Timeframe: 12 months

Number of Participants With Serious Adverse Events

Intervention	months (Median)
DSF-Cu	1.7

Number of Participants with Grade 3 and 4 serious adverse events (NCT03034135)
Timeframe: 14 months

Progression Free Survival

Intervention	Participants (Count of Participants)
DSF-Cu	2

Percentage of patients that are free from progressive disease per RANO criteria (NCT03034135)
Timeframe: 6 months

Objective Response Rate

Intervention	percentage of participants (Number)
DSF-Cu	14

ORR will be defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RANO criteria. (NCT03034135)
Timeframe: 6 months

Overall Survival

Intervention	Participants (Count of Participants)
	Complete response	Partial Response
DSF-Cu	0	0

Percentage of patients that are alive (NCT03034135)
Timeframe: 6 months and 12 months

Article	Year
Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma - a systematic literature review. Expert opinion on drug delivery, 2023, Volume: 20, Issue:4 Topics: Brain; Brain Neoplasms; Disulfiram; Drug Delivery Systems; Glioblastoma; Humans	2023
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. Oncotarget, 2013, Volume: 4, Issue:4 Topics: Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Artemisinins; Auranofin; Brain Neoplasms	2013
Concise review: bullseye: targeting cancer stem cells to improve the treatment of gliomas by repurposing disulfiram. Stem cells (Dayton, Ohio), 2015, Volume: 33, Issue:4 Topics: Animals; Brain Neoplasms; Clinical Trials as Topic; Disulfiram; Drug Delivery Systems; Drug Repositi	2015
Matrix metalloproteinase-2 and -9 in glioblastoma: a trio of old drugs-captopril, disulfiram and nelfinavir-are inhibitors with potential as adjunctive treatments in glioblastoma. Archives of medical research, 2012, Volume: 43, Issue:3 Topics: Angiotensin-Converting Enzyme Inhibitors; Brain Neoplasms; Captopril; Chemotherapy, Adjuvant; Disulf	2012
Brain research and violent behavior. A summary and evaluation of the status of biomedical research on brain and aggressive violent behavior. Archives of neurology, 1974, Volume: 30, Issue:1 Topics: Aggression; Animals; Anticonvulsants; Antidepressive Agents; Behavior, Animal; Bipolar Disorder; Bra	1974

Article	Year
Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma. Journal of neuro-oncology, 2018, Volume: 138, Issue:1 Topics: Adjuvants, Immunologic; Adult; Aged; Antineoplastic Agents; Brain Neoplasms; Cohort Studies; Copper;	2018
A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma. Journal of neuro-oncology, 2019, Volume: 142, Issue:3 Topics: Acetaldehyde Dehydrogenase Inhibitors; Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplasti	2019

Article	Year
Disulfiram and copper combination therapy targets NPL4, cancer stem cells and extends survival in a medulloblastoma model. PloS one, 2021, Volume: 16, Issue:11 Topics: Aldehyde Dehydrogenase; Animals; Apoptosis; Brain Neoplasms; Cell Cycle; Cell Proliferation; Copper;	2021
PLGA-Nano-Encapsulated Disulfiram Inhibits Hypoxia-Induced NF-κB, Cancer Stem Cells, and Targets Glioblastoma In Vitro and In Vivo. Molecular cancer therapeutics, 2022, 08-02, Volume: 21, Issue:8 Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Disulfiram; Glioblastoma; Humans; Hypoxia; Mice; Neoplas	2022
Disulfiram potentiates the anticancer effect of cisplatin in atypical teratoid/rhabdoid tumors (AT/RT). Cancer letters, 2020, 08-28, Volume: 486 Topics: Activating Transcription Factor 3; Aldehyde Dehydrogenase; Animals; Brain Neoplasms; Cell Line, Tumo	2020
Repositioning disulfiram as a radiosensitizer against atypical teratoid/rhabdoid tumor. Neuro-oncology, 2017, Aug-01, Volume: 19, Issue:8 Topics: Animals; Apoptosis; Brain Neoplasms; Cell Cycle Checkpoints; Cell Proliferation; Disulfiram; Humans;	2017
Blocking distinct interactions between Glioblastoma cells and their tissue microenvironment: A novel multi-targeted therapeutic approach. Scientific reports, 2018, 04-03, Volume: 8, Issue:1 Topics: Acetaldehyde Dehydrogenase Inhibitors; Animals; Anti-Ulcer Agents; Apoptosis; Brain Neoplasms; Carbe	2018
Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro. Cancer research and treatment, 2019, Volume: 51, Issue:2 Topics: Acetaldehyde Dehydrogenase Inhibitors; Brain Neoplasms; Caspase 3; Cell Cycle; Cell Line, Tumor; Dis	2019
The efficacy of a coordinated pharmacological blockade in glioblastoma stem cells with nine repurposed drugs using the CUSP9 strategy. Journal of cancer research and clinical oncology, 2019, Volume: 145, Issue:6 Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Auranofin; Brain Neoplasms; Cap	2019
How could a drug used to treat alcoholism also be effective against glioblastoma? Expert review of anticancer therapy, 2013, Volume: 13, Issue:3 Topics: Alcohol Deterrents; Alcoholism; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Disulfi	2013
Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage. Carcinogenesis, 2014, Volume: 35, Issue:3 Topics: Animals; Antineoplastic Agents, Alkylating; Brain; Brain Neoplasms; Cell Line, Tumor; Disulfiram; DN	2014
CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide. Oncotarget, 2014, Sep-30, Volume: 5, Issue:18 Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Artemisinins; Artesunate; Auran	2014
Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors. Neuro-oncology, 2015, Volume: 17, Issue:6 Topics: Acetaldehyde Dehydrogenase Inhibitors; Aldehyde Dehydrogenase; Animals; Antineoplastic Agents; Apopt	2015
Development of disulfiram-loaded poly(lactic-co-glycolic acid) wafers for the localised treatment of glioblastoma multiforme: a comparison of manufacturing techniques. Journal of pharmaceutical sciences, 2015, Volume: 104, Issue:3 Topics: Antineoplastic Agents; Brain Neoplasms; Calorimetry, Differential Scanning; Cell Line, Tumor; Cell S	2015
Hot melt extruded and injection moulded disulfiram-loaded PLGA millirods for the treatment of glioblastoma multiforme via stereotactic injection. International journal of pharmaceutics, 2015, Oct-15, Volume: 494, Issue:1 Topics: Brain Neoplasms; Cell Line, Tumor; Disulfiram; Drug Carriers; Drug Delivery Systems; Freezing; Gliob	2015
Suppressing glioblastoma stem cell function by aldehyde dehydrogenase inhibition with chloramphenicol or disulfiram as a new treatment adjunct: an hypothesis. Current stem cell research & therapy, 2009, Volume: 4, Issue:4 Topics: Aldehyde Dehydrogenase; Animals; Brain Neoplasms; Cell Differentiation; Cell Division; Chemotherapy,	2009
Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. British journal of cancer, 2012, Oct-23, Volume: 107, Issue:9 Topics: Aldehyde Dehydrogenase; Apoptosis; Brain Neoplasms; Cell Line, Tumor; Copper; Cytotoxicity, Immunolo	2012
Disulfiram, a drug widely used to control alcoholism, suppresses the self-renewal of glioblastoma and over-rides resistance to temozolomide. Oncotarget, 2012, Volume: 3, Issue:10 Topics: Alcohol Deterrents; Antineoplastic Agents, Alkylating; Apoptosis; Blotting, Western; Brain Neoplasms	2012
High-throughput chemical screens identify disulfiram as an inhibitor of human glioblastoma stem cells. Oncotarget, 2012, Volume: 3, Issue:10 Topics: Alcohol Deterrents; Animals; Apoptosis; Blotting, Western; Brain Neoplasms; Cell Proliferation; Disu	2012
Comment on 'cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells'. British journal of cancer, 2013, Mar-05, Volume: 108, Issue:4 Topics: Aldehyde Dehydrogenase; Brain Neoplasms; Copper; Disulfiram; Glioblastoma; Humans; Neoplastic Stem C	2013
Reply: Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. British journal of cancer, 2013, Mar-05, Volume: 108, Issue:4 Topics: Aldehyde Dehydrogenase; Brain Neoplasms; Copper; Disulfiram; Glioblastoma; Humans; Neoplastic Stem C	2013
Cu/Zn superoxide dismutase plays a role in angiogenesis. International journal of cancer, 2002, Jan-01, Volume: 97, Issue:1 Topics: Animals; Apoptosis; Brain Neoplasms; Carcinoma, Lewis Lung; Disulfiram; Endothelium, Vascular; Enzym	2002

disulfiram and Benign Neoplasms, Brain