Patient education materials (PEM)s were extracted from provincial cancer agencies to determine their organizational health literacy by evaluating the quality, actionability, and functional accessibility (e.g., readability and understandability) of their PEMs. PEMs from 10 provincial agencies were assessed for their grade reading level (GRL), using eight numerical and two graphical readability scales, and underwent a difficult word analysis. The agencies were assessed for PEM quality using two methods (JAMA benchmarks and DISCERN), while actionability and understandability were assessed using the Patient Education Materials Assessment Tool (PEMAT). Seven hundred and eighty-six PEMs were analyzed. The overall average GRL was 9.3 ± 2.1, which is above the recommended 7th GRL for health information. The difficult word analysis showed that 15.4% ± 5.1% of texts contained complex words, 35.8% ± 6.8% of texts contained long words, and 24.2% ± 6.6% of texts contained unfamiliar words. Additionally, there was high overlap between the most frequently identified difficult words in the PEMs and the most frequently misunderstood words by cancer patients identified in the literature. Regarding quality indicators, no agency displayed all four indicators according to the JAMA benchmarks and DISCERN scores ranged between 38 (poor) to 66 (excellent). PEMAT scores ranged between 68% to 88% for understandability and 57% to 88% for actionability. PEMs continue to be written at a level above the recommended GRL across all provinces, and there was overall high variability in the quality, understandability, and actionability of PEMs among provincial agencies. This represents an opportunity to optimize materials, thus ensuring understanding by a wider audience and improving health literacy among Canadian cancer patients.

Disulfiram, traditionally used as an alcohol-aversion drug, has demonstrated anticancer properties attributed to its metabolism into diethyldithiocarbamate (DDC), a potent copper-binding agent. Previously, we developed a liposomal formulation of copper diethyldithiocarbamate (Cu(DDC)₂) by incorporating DDC into copper-containing liposomes. In this study, we present an improved formulation achieved by directly mixing DDC and copper in a suspension of empty liposomes, leveraging DDC's copper ionophore-like activity. This method minimizes Cu(DDC)₂ precipitation outside the liposomes and enables efficient drug loading at defined molar ratios. The formulation effectively slowed the growth of subcutaneous MDA-MB-231 tumors in mice and showed increased efficacy in 4T1 tumors in immunocompetent mice compared to immunocompromised counterparts. In vitro, Cu(DDC)₂-treated cancer cells exhibited upregulation of damage-associated molecular patterns (DAMPs), including ATP release, HMGB1 secretion, and calreticulin exposure. Transcriptomic analysis revealed increased expression of immune activation and copper transport genes, further supporting the potential for immunogenic cell death (ICD) induction. In a prophylactic tumor vaccination model, inoculation with Cu(DDC)₂-treated CT26 cells delayed tumor growth and conferred protection in a subset of animals, indicating the induction of an adaptive immune response consistent with ICD. These findings align with previous reports of disulfiram-induced ICD and provide functional validation linking this activity to DDC's role as a copper ionophore. This formulation offers a robust and scalable platform for exploring the role of copper as an immune modulator and lays the groundwork for future optimization toward clinical application.

Copper-binding agents can trigger immunogenic cell death (ICD) and modulate responses to immune checkpoint inhibitors (ICIs), but how tumor copper biology, agent chemistry, and tumor microenvironment shape these effects is unclear. We evaluated diethyldithiocarbamate [Cu(DDC)₂] and clioquinol [Cu(CQ)₂] in two syngeneic colorectal cancer models with distinct copper handling. In vitro transcriptomic and cytokine profiling showed compound-specific activation of cuproptosis and immune pathways. In vivo, copper accumulation and isotopic fractionation correlated with immune features of the tumor microenvironment, including immune cell infiltration and calreticulin exposure. In CT26 tumors, Cu(CQ)₂ transiently enhanced programmed cell death protein 1 (PD-1) blockade, then promoted immune suppression with prolonged dosing. In MC38 tumors, combination therapy showed sustained antagonism or no added benefit. These data indicate that tumor-intrinsic copper handling and ionophore identity jointly determine immune dynamics and therapeutic outcome, and they suggest copper isotopic metrics as candidate biomarkers warranting further evaluation in the context of copper-based strategies with ICIs.

Copper (Cu) is an essential element required by all living cells, where it supports critical enzymatic and signaling functions. In cancer, this balance is often disrupted, creating vulnerabilities that can be therapeutically exploited. Changes in Cu availability have been shown to influence key immunoregulatory pathways, including those involved in inflammation, cell death, and immune evasion. Notably, Cu can drive expression of programmed death ligand 1 (PD-L1), contributing to immunosuppression, while also promoting immunogenic cell death, which stimulates adaptive immune responses. These dual effects highlight the complexity and therapeutic potential of Cu-based interventions, particularly in the context of immune modulation and toxicity. This review argues that Cu-based nanomedicines can selectively deliver high concentrations of bioactive Cu to tumor cells, inducing cell death and triggering adaptive immune responses. We summarize current knowledge on Cu’s roles in cancer and immunity, emphasizing recent insights into how these intersect through Cu-mediated modulation of anticancer immune pathways. Finally, we explore the clinical potential of Cu-based nanomedicines to convert immunologically “cold” tumors into “hot” ones, thereby improving responses to immunotherapy. Realizing this potential will depend on the thoughtful integration of Cu delivery approaches with existing immunotherapeutic strategies.

Copper (Cu) is an essential mineral required by all living cells, where it supports critical enzymatic and signaling functions. In cancer, this balance is often disrupted, creating vulnerabilities that can be therapeutically exploited. Changes in Cu availability have been shown to influence key immunoregulatory pathways, including those involved in inflammation, cell death, and immune evasion. Notably, Cu can drive expression of programmed death-ligand 1 (PD-L1), contributing to immunosuppression, while also promoting immunogenic cell death, which stimulates adaptive immune responses. These dual effects highlight the complexity and therapeutic potential of Cu-based interventions, particularly in the context of immune modulation and toxicity. This review argues that Cu-based nanomedicines can selectively deliver high concentrations of bioactive Cu to tumor cells, inducing cell death and triggering adaptive immune responses. We summarize current knowledge on Cu’s roles in cancer and immunity, emphasizing recent insights into how these intersect through Cu-mediated modulation of anti-cancer immune pathways. Finally, we explore the clinical potential of Cu-based nanomedicines to convert immunologically “cold” tumors into “hot” ones, thereby improving responses to immunotherapy. Realizing this potential will depend on the thoughtful integration of Cu delivery approaches with existing immunotherapeutic strategies.