DCA amplified PDT-induced oxidative stress, overcoming redox defenses and enhancing ferroptotic and immunogenic responses. These findings suggest that combining DCA with PDT enhances multimodal cell death in PDAC, providing a rationale for further in vivo studies to validate this redox-metabolic approach to treating chemoresistant pancreatic tumors.

In this study, 20 new derivatives were designed and synthesized through further structural optimization of the dichloroacetate (DCA) derivatives, and their inhibitory effects on PDK1 and anticancer activities were systematically evaluated...Importantly, low-dose D16 (20 mg/kg) robustly inhibited tumor growth in vivo without systemic toxicity. These findings establish D16 as a potent PDK1 inhibitor that shifts tumor metabolism, offering a promising therapeutic approach for cancer treatment.

Furthermore, predictive modeling and molecular docking revealed that tumors with elevated CENPW levels exhibited enhanced sensitivity to targeted therapies such as OSU-03012 and rapamycin. Collectively, our findings indicate that CENPW acts as a potential oncogenic regulator in KIRC, influencing both immune pathways and therapeutic responsiveness, and may serve as a novel biomarker and treatment target.

2 mM NaVPA-3 mM NaDCA, as well as temozolomide, had individual impacts on the SLC12A2, SLC12A5, CDH1, CDH2, EZH2, and GFAP expressions of tested GBM5-1, GBM5-2F, and GBM5-3F primary cells of female GBM patients. The combination of 2 mM NaVPA-3 mM NaDCA may have an advantage in antitumor activity and may be more effective than TMZ; however, the effect is individual.

The findings suggest PDK1 as a critical regulator of glycolytic metabolism and a potential therapeutic target in osteosarcoma. Targeting PDK1 could provide a novel therapeutic strategy for treating osteosarcoma and possibly other cancers.

It is well-established that pyruvate dehydrogenase kinase (PDK)-mediated phosphorylation of PDH leads to its inactivation and that dichloroacetic acid (DCA), a PDK inhibitor, has been investigated in preclinical and early clinical studies as a potential therapeutic agent for lung cancer. This study aims to elucidate how PLK1-associated activity drives the metabolic reprogramming from OXPHOS to glycolysis during cellular transformation, thereby contributing to lung carcinogenesis. Our results provide support for a clinical trial to evaluate the efficacy of Onvansertib plus DCA in treating lung cancer.

The chemotherapy drug called Adriamycin, often known as doxorubicin (Dox), is used to treat BC, including late stages. ABCG2 mRNA expression is markedly upregulated in MCF7 cells upon P53 and ERK5 downregulation. Collectively, these findings showed that DCA increases the susceptibility of breast cancer cells to Dox through the upregulation of NKG2DL and the downregulation of ABCG2 expression via a p53-ERK5 dependent pathway.

Here, we explored the rationale behind combining TKIs with an inhibitor of glucose metabolism (dichloroacetate, DCA), focusing on the synergistic effects from dual inhibition of oncogenic and metabolic reprogramming...These changes in tumor behaviour leads to a higher pro-apoptotic status responsible for an increased tumor response and, in parallel, the lower doses reduced alternative evasion pathways contributing to decrease of tumor invasion and resistance mechanism. This study shed light on a new potential combined therapeutic approach to improve clinical outcomes in targeted cancer therapy scenarios.

The data suggest that VPA-NaDCA has a more effective impact than TMZ; however, the effect of investigational medicines on carcinogenesis varies depending on the cell line. The study of the efficacy of drugs used to treat tumors on the CAM and cells demonstrates that it is essential to assess the effectiveness of treatment, which should be personalized, before administering chemotherapy.

Specifically, water-soluble small molecular dichloroacetate is rapidly released to redirect tumor cell metabolism from glycolysis to oxidative phosphorylation, thereby reducing lactic acid accumulation, restricting glucose uptake, and enhancing the susceptibility of cancer cells to mitochondrial damage...In 4T1 subcutaneous tumor models, SeqGel effectively suppressed tumor growth and markedly reduced lung and lymph node metastases by promoting CD8+ T cell infiltration and depleting regulatory T cells. This study establishes a paradigm for metabolic-immune synergy, offering a promising strategy for targeting aggressive cancers through chrono-metabolic immunotherapy.

A similar trend was observed in mice bearing patient-derived neurospheres. These findings highlight BDNP as a promising strategy for GBM therapy and establish valuable protocols for developing and validating novel multidrug nanoparticles, especially for antibodies and small molecule cocktails.

Notably, AS1411/LNP-si circPDHK1 successfully inhibited the phosphorylation of the mTOR-AKT pathway, suppressed the proliferation and migration of ccRCC cells, and exhibited minimal side effects in vital organs. Taken together, the aptamer-guided LNP loaded siRNA targeting circPDHK1 (AS1411/LNP-si circPDHK1) displays great potential for ccRCC therapy.