Syrosingopine treatment sensitizes LUAD cells to PARP inhibitor (PARPi) and potentiates the therapeutic efficacy of olaparib in a mouse LUAD model. Altogether, our study reveals that lactylation drives RIG-I nuclear function to inhibit DNA damage repair via PARP suppression. This supports the potential co-administration of syrosingopine and PARPi for LUAD treatment.

Alone or combined with inhibition of mitochondrial respiration by metformin and phenformin, the MCT4 inhibitor syrosingopine significantly inhibits lactate efflux, induces cell viability reduction in four different RCC cell lines and patient-derived 2D/3D models, and alterations in cellular metabolism and mitochondrial respiration. Six patient-derived RCC air-liquid interface models, mimicking the complex RCC architecture, corroborate these data. Beyond potential prediction of patient outcome using MCT4 expression and DNA methylation at specific CpG sites, drug targeting of MCT4 and inhibiting mitochondrial respiration synergistically is a novel treatment strategy for metastatic ccRCC.

Furthermore, pharmacological studies revealed that metformin combined with copanlisib significantly inhibited tumors by blocking the energy metabolism pathways PI3K/AKT and AMPK/mTOR. Rationally, targeting multiple nodes along the ENO1-ATP/lactate-AMPK/PI3K/AKT-mTOR axis may be effective for GC treatment, as indicated by the significant suppression of tumor growth by metformin (which inhibits ATP production) plus syrosingopine (which disrupts lactate homeostasis). In conclusion, the complex interplay between metabolism and tumor stemness offers novel therapeutic directions and potential treatment strategies for GC.

Our study found that SLC16A3 is closely related to HBV status and liver cancer, and it has a significant marker for the prognosis of HBV-positive liver cancer. SLC16A3 is associated with abnormal metabolic pattern and immune regulation of Kupffer cells, and can directly affect HBV-positive hepatocellular carcinoma cell lines.

The results indicated the role of MCT1/4 in the pathobiology of GBM and the diagnostic utility at the immunohistochemical level. Syrosingopine, an antihypertensive agent with good CNS penetration and previously used in different malignancies, may be an essential therapeutic adjunct in GBM.

The DCA curve showed that the model had a notable clinical application value. High expression of MCT4 is associated with poor prognosis and reduced efficacy of immunotherapy in patients with advanced LUAD.

And SLC16A3 inhibitors significantly suppressed the proliferation of HCC, while simultaneously enhancing T-cell cytotoxicity and reducing exhaustion. These results reveal the phenomenon of immune escape mediated by metabolic reprogramming and suggest that SLC16A3 may serve as a novel target for intervention.

Furthermore, a preliminary analysis of an animal study reveals that Capsaicin significantly suppressed the growth of Hep3B cells inoculated in BALB/c nude mice without hurting body weight, liver, and spleen. Our findings provide novel evidence that Capsaicin exerts apoptotic and anti-Warburg effect via c-Myc/MCT4 signaling axis as a potent anticancer candidate for liver cancer therapy.

Finally, X-ray crystallographic studies highlight unique interactions between BGal2C and a CAIX-mimic that are not observed within the CAII active site and which may underlie the strong specificity of BGal2C for CAIX. These studies demonstrate the utility of a novel sulfonamide in interfering with elevated proton and lactate flux, a hallmark of many solid tumors.

So, we draw a conclude that SLC16A3 is associated with poor prognosis of HCC. Inhibition of SLC16A3 expression is a potential therapeutic target for HCC.

Overexpression of SLC16A3 is an independent prognostic factor in patients with BC. SLC16A3 may influence the immune infiltration of BC by regulating BC metabolism and m6A methylation, which ultimately can lead to the progress of BC. For the detection and therapy of BC, SLC16A3 may be a potent therapeutic target for BC.

Genetic and pharmacological inhibition of Slc16a3 dramatically reduced the glycolytic activity and lactic acid production in tumor cells, and ameliorated the immunosuppressive tumor microenvironments (TMEs), leading to boosted antitumor effects via anti-PD-1 blockade. Our study therefore demonstrates that tumor cell-intrinsic SLC16A3 may be a potential target to reverse tumor resistance to immunotherapy.