Disulfiram: Side Effects and Toxicity

Sousa, Avinash De

doi:10.1007/978-981-32-9876-7_7

Cited by 4 publications

(1 citation statement)

References 53 publications

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“…The most obvious choice would be the targeting of ALDH1A1 itself. There are drugs already available broadly inhibiting aldehyde dehydrogenases (e.g., disulfiram), which unfortunately can show severe side effects and toxicity ( 45 ). Isoform-specific inhibitors are under development ( 23 ), but their safety profile remain to be elucidated under the premise that ALDH1A1 is also expressed during development and in the adult brain ( 27, 46 ).…”

Section: Discussionmentioning

confidence: 99%

A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma

Kebir

Ullrich

Berger

et al. 2022

Clinical Cancer Research

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Purpose: Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly target tumor cells that can survive, adapt, and subclonally expand under primary therapy. Experimental Design: To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy. We further used two independent validation cohorts of paired clinical tissues to test our findings. Follow-up preclinical treatment strategies were evaluated in patient-derived xenografts. Results: We describe, in clinical samples, an archetype of rare ALDH1A1+ tumor cells that enrich and acquire AKT-mediated drug resistance in response to standard-of-care temozolomide. Importantly, we observe that drug resistance of ALDH1A1+ cells is not intrinsic, but rather an adaptive mechanism emerging exclusively after temozolomide treatment. In patient cells and xenograft models of disease, we recapitulate the enrichment of ALDH1A1+ cells under the influence of temozolomide. We demonstrate that their subclonal progression is AKT-driven and can be interfered with by well-timed sequential rather than simultaneous antitumor combination strategy. Conclusion: Drug-resistant ALDH1A1+/pAKT+ subclones accumulate in patient tissues upon adaptation to temozolomide therapy. These subclones may therefore represent a dynamic target in glioblastoma. Our study proposes the combination of temozolomide and AKT inhibitors in a sequential treatment schedule as a rationale for future clinical investigation.

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Section: Discussionmentioning

confidence: 99%

A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma

Kebir

Ullrich

Berger

et al. 2022

Clinical Cancer Research

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Addiction and Liver Disease: Exploring the Complex Relationship and Implications for Clinical Management

Hudson,

Howarth,

Idalsoaga

et al. 2024

Curr Hepatology Rep

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Understanding Indian Doctors’ Attitudes Toward Alcohol Pharmacotherapy and Prescription: A Mediational Analysis

Ghosh,

Modak,

Rozatkar

2024

Indian Journal of Psychological Medicine

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Background: Alcohol use disorder (AUD) causes significant morbidity and mortality. Prescription of AUD pharmacotherapies remains low. Attitudes toward AUD pharmacotherapies influence their prescription rates. We conducted an online survey to assess how attitudes modulate the association between knowledge and prescription rates for four commonly used AUD medications among Indian clinicians. Methods: An online survey was sent nationwide to Indian physicians between February and April 2023 to assess knowledge, attitudes, and practices of various AUD medications. An a priori model was defined to indicate the relationship between study variables. Bootstrapped correlation analysis was conducted to determine confidence intervals of the correlation coefficients between knowledge, attitudes, and prescription practices. Additional subgroup analysis was conducted for faculty and private psychiatrists to assess if they prescribed differently. Results: A total of 387 physicians responded to the survey. Bootstrapped correlation analysis indicated that safety and acceptability played a moderated prescription rates for acamprosate and naltrexone while they mediating role among faculty. For Disulfiram, perceived efficacy had a mediating effect, especially among private psychiatrists. Among faculty, perceived safety negatively mediated Disulfiram prescriptions. There was no indirect effect of attitudes on the association between knowledge and prescription practices for Baclofen. Conclusion: The role of attitudes varied across medications. For acamprosate and naltrexone, perceived safety and acceptability significantly moderated prescription rates. For Disulfiram, perceived efficacy played a significant mediating effect. Attitudes did not influence Baclofen prescriptions as a whole, but acceptability significantly mediated prescriptions for private psychiatrists. This might indicate that physicians prescribe Baclofen as an ineluctable option.

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Disulfiram: Side Effects and Toxicity

Cited by 4 publications

References 53 publications

A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma

A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma

Addiction and Liver Disease: Exploring the Complex Relationship and Implications for Clinical Management

Understanding Indian Doctors’ Attitudes Toward Alcohol Pharmacotherapy and Prescription: A Mediational Analysis

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