Repurposing drugs in oncology (ReDO)—selective PDE5 inhibitors as

Pantziarka, Pan; Sukhatme, Vidula; Crispino, Sergio; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P.

doi:10.3332/ecancer.2018.824

Cited by 61 publications

(73 citation statements)

References 109 publications

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“…After a novel compound is identified or designed, preclinical and clinical data from phase I, II and III clinical trials are generated prior to approval. Drug repurposing represents the identification of the novel pharmacological effects of conventional drugs (2). As the pharmacokinetics, pharmacodynamics and safety in humans have already been established, expanding the application of a drug to additional diseases has advantages in terms of cost and time efficiency.…”

Section: Introductionmentioning

confidence: 99%

Repurposing itraconazole as an anticancer agent

et al. 2017

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Abstract. Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/β-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent.

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Section: Introductionmentioning

confidence: 99%

Repurposing itraconazole as an anticancer agent

et al. 2017

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“…International Publisher metformin, aspirin, hydroxychloroquine and thalidomide [3,4]. Several drugs investigated for repurposing in oncology are anthelminthics which have been in clinical use against different worms for several decades [6,7].…”

Section: Ivyspringmentioning

confidence: 99%

“…Well-characterized drugs may come with detailed knowledge of their pharmacodynamics, pharmacokinetics and side effects as well as with established regimens for clinical applications. In favorable cases, this will result in short-circuiting of the preclinical phase of the drug development [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Candidates may reveal another mode of action against cancer cells than in their original indication and require different concentrations to exhibit efficacy in antitumor regimens. Furthermore, they may be cytotoxic or may instead exert an anticancer effect by acting on one or more aspects of the tumor microenvironment either alone or in combination with existing anticancer treatments [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Examples of drugs identified as high-potential agents within the Repurposing Drugs in Oncology (ReDO) project include mebendazole, cimetidine, nitroglycerin, diclofenac and clarithromycin, among others [3]. Distinct non-cancer drugs already investigated in clinical cancer trials comprise…”

Section: Introductionmentioning

confidence: 99%

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Repurposing of Anthelminthics as Anticancer Drugs

Hamilton¹,

Rath²

2018

Oncomedicine

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Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma

et al. 2023

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ImportanceDisulfiram has demonstrated broad antitumoral effect in several preclinical studies. One of the proposed indications is for the treatment of glioblastoma.ObjectiveTo evaluate the efficacy and safety of disulfiram and copper as add-on to alkylating chemotherapy in patients with recurrent glioblastoma.Design, Setting, and ParticipantsThis was a multicenter, open-label, randomized phase II/III clinical trial with parallel group design. Patients were recruited at 7 study sites in Sweden and 2 sites in Norway between January 2017 and November 2020. Eligible patients were 18 years or older, had a first recurrence of glioblastoma, and indication for treatment with alkylating chemotherapy. Patients were followed up until death or a maximum of 24 months. The date of final follow-up was January 15, 2021. Data analysis was performed from February to September 2022.InterventionsPatients were randomized 1:1 to receive either standard-of-care (SOC) alkylating chemotherapy alone, or SOC with the addition of disulfiram (400 mg daily) and copper (2.5 mg daily).Main Outcomes and MeasuresThe primary end point was survival at 6 months. Secondary end points included overall survival, progression-free survival, adverse events, and patient-reported quality of life.ResultsAmong the 88 patients randomized to either SOC (n = 45) or SOC plus disulfiram and copper (n = 43), 63 (72%) were male; the mean (SD) age was 55.4 (11.5) years. There was no significant difference between the study groups (SOC vs SOC plus disulfiram and copper) in 6 months survival (62% [26 of 42] vs 44% [19 of 43]; P = .10). Median overall survival was 8.2 months (95% CI, 5.4-10.2 months) with SOC and 5.5 months (95% CI, 3.9-9.3 months) with SOC plus disulfiram and copper, and median progression-free survival was 2.6 months (95% CI, 2.4-4.6 months) vs 2.3 months (95% CI, 1.7-2.6 months), respectively. More patients in the SOC plus disulfiram and copper group had adverse events grade 3 or higher (34% [14 of 41] vs 11% [5 of 44]; P = .02) and serious adverse events (41% [17 of 41] vs 16% [7 of 44]; P = .02), and 10 patients (24%) discontinued disulfiram treatment because of adverse effects.Conclusions and RelevanceThis randomized clinical trial found that among patients with recurrent glioblastoma, the addition of disulfiram and copper to chemotherapy, compared with chemotherapy alone, resulted in significantly increased toxic effects, but no significant difference in survival. These findings suggest that disulfiram and copper is without benefit in patients with recurrent glioblastoma.Trial RegistrationClinicalTrials.gov Identifier: NCT02678975; EUDRACT Identifier: 2016-000167-16

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Repurposing drugs in oncology (ReDO)—selective PDE5 inhibitors as

Cited by 61 publications

References 109 publications

Repurposing itraconazole as an anticancer agent

Repurposing itraconazole as an anticancer agent

Repurposing of Anthelminthics as Anticancer Drugs

Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma

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