Abstract 5738: Repurposing disulfiram for cancer: A drug delivery and population-based approach
Bibliographic record
Abstract
Abstract Purpose: Disulfiram was approved by the FDA for treatment of alcohol abuse in 1951, although for over 40 years there has been evidence supporting disulfiram’s use as an anti-cancer drug. Upon administration, disulfiram is hydrolyzed to form two molecules of DDC, which upon binding Cu forms Cu(DDC)2, the proposed active form against cancer. It was our goal to formulate the water-insoluble Cu(DDC)2 in liposomes to facilitate its repurposing for breast and colon cancers. In addition, we also initiated an ongoing population-based study assessing the protective and treatment effects of disulfiram with cancer. Methods: Cu(DDC)2 liposomes were generated by the thin-film hydration method followed by extrusion, using DSPC and cholesterol (55:45 molar ratio). DDC and CuSO4 were added to the liposomes forming Cu(DDC)2, which was transported inside the liposomes. Anti-tumor activity was evaluated in tumor-bearing mice with or without competent immune systems, and immune system activation was assessed via a cancer vaccination model and the expression of markers of immunogenic cell death (ICD). A study was also initiated for cancer cases and controls in British Columbia (BC Cancer) with at least one prescription of disulfiram from 1996-2022 (PharmaNET), patients treated with immune-modulating therapies (BC Cancer), and outcome of death (Vital Statistics). Results: Liposomes encapsulating Cu(DDC)2 had a size of 100 nm and polydispersity of 0.1, and caused a 40% reduction in tumor burden in a MDA-MB-231 xenograft model. In a syngeneic tumor model of breast cancer the response with immune-competent mice was greater than mice lacking immune function, and a cancer vaccination model and the presence of ATP, HMBG1 and surface-exposed calreticulin indicated the presence of ICD. Conclusions: Cu(DDC)2 was formulated in liposomes facilitating its parenteral administration, and its anti-cancer activity was found to be due in part to activation of the adaptive immune system through ICD. A case-control study is currently being employed to examine the clinical potential of disulfiram, as a protectant and as an adjuvant with immune-activating therapies such as checkpoint inhibitors and anthracyclines to potentially improve efficacy through induction of ICD. Citation Format: Devon Heroux, Ada W. Leung, Roger Gilabert-Oriol, Marcel B. Bally. Repurposing disulfiram for cancer: A drug delivery and population-based approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5738.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".