DLAT (Dihydrolipoamide S-Acetyltransferase)

These results suggest that TP may both inhibit the glycolysis of CRC and induce cuprotosis via the Hexokinase 2 (HK2)/Dihydrolipoamide S-acetyltransferase (DLAT) pathway. Future research should systematically verify its effectiveness and safety through in vivo studies and clinical trials to promote the application of TP in CRC treatment.

Drug sensitivity analysis revealed that the high-risk group was more sensitive to fluorouracil and gemcitabine (P<0.001), whereas the low-risk group showed better responses to regorafenib (P=0.007). This study establishes a novel prognostic model for COAD based on cofactor and vitamin metabolism, enabling precise survival prediction and guiding personalized therapeutic strategies. The model underscores the interplay between metabolic-immune crosstalk and chemotherapy response heterogeneity, providing a framework for developing targeted metabolic therapies combined with immune modulation.

Importantly, this nanoplatform effectively targeted stubborn breast CSCs, exhibiting an IC50 as low as 13.70 ± 0.36 μg/mL─attributed to the mitochondrial targeting and subsequent inhibition of robust oxidative phosphorylation within CSCs, which rely more heavily on this pathway than on glycolysis compared to conventional cancer cells. In summary, this work presents a novel "multi-targeting" therapeutic strategy that orchestrates mitochondrial dysfunction, cuproptosis, apoptosis, and pyroptosis via a chemo-photothermal combination, offering a robust and broad-spectrum approach to eradicate both conventional resistant cancer cells and refractory CSCs.

DLAT plays a critical role in CRC progression and treatment response, demonstrating potential as a prognostic biomarker and therapeutic target.

The nanoparticles exhibit potent antitumor efficacy in vivo, underscoring the potential of exploiting metabolic vulnerabilities to enhance cuproptosis. This study introduces a novel therapeutic avenue that leverages metabolic reprogramming to initiate regulated cell death pathways in cancer treatment.

These findings suggest that anti-DLAT AAb shows potential for BC diagnosis, especially among individuals under 45 years old. Besides, multicenter validation should be carried out to confirm this finding in the future.

KCNQ1 is a tumor suppressor of CRC that is DNA methylated. DHZCP in combination with KCNQ1 overexpression exhibits anti-CRC effects through the regulation of cuproptosis-related pathways, cuproptosis is promoted, oxidative stress is enhanced, and copper accumulates, thus supporting the clinical application prospects of DHZCP in CRC.

In vivo, DCTH showed enhanced tumor targeting, effective photothermal response, significant tumor growth inhibition, immunogenic cell death (ICD) induction, dendritic cell maturation, and increased cytotoxic T-cell infiltration. Overall, DCTH presents a modular and intelligent nanotherapeutic platform leveraging metal-gas synergy to overcome TME-associated therapeutic resistance and achieve multimodal antitumor therapy.

The Cu-Cur DTLPs developed in this study effectively induce copper-mediated death in TNBC through a dual-targeted delivery system, significantly enhancing antitumor activity with favorable safety profiles. This establishes a highly promising novel nanotherapeutic strategy for TNBC treatment.

Next, two gastric cancer cell lines (AGS, HGC27) were selected for in vitro experiments to assess the combined effects of PUN and the copper ionophore elesclomol (ES) (hereafter referred to as ES-Cu, representing the combination of ES and Cu2+)...In combination therapy strategies, PUN can work synergistically with chemotherapy drugs to suppress gastric cancer growth. Furthermore, PUN enhances its inhibitory effect on gastric cancer by working synergistically with cuproptosis through targeting FDX1.

Additionally, NaOx elevated cuproptosis in HK-2 cells, and this elevation was blocked by ZnT1 over-expression, which in turn was reversed by TTM, a cuproptosis inhibitor. This study provided evidence that Ro mitigated cuproptosis HK-2 cells induced by high oxalate through inhibiting ZnT1, thus effectively suppressing oxidative stress and crystal deposition triggered by high oxalate.