New insights into molecular chaperone TRAP1 as a feasible target for future cancer treatments.

Tumor necrosis factor receptor-associated protein 1 (TRAP1), a molecular chaperone, is a major member of the mitochondrial heat shock protein 90 (Hsp90) family. Studies have shown that TRAP1 can prevent hypoxia-induced damage to cardiomyocytes, maintain cardiomyocytes viability and mitochondrial membrane potential, and protect cardiomyocytes. In addition, it can also protect astrocytes from ischemic damage in vitro. In recent years, there have been many new discoveries in tumors. The abnormal expression of TRAP1 is closely related to the occurrence and development of various tumors. TRAP1 protein seems to be a central regulatory protein, involved in the activation of various oncogenic proteins and signaling pathways, and has a balanced function at tumor transformation and the intersection of different metabolic processes. Targeting its chaperone activity and molecular interactions can destroy the metabolism and survival adaptability of tumor cells, paving the way for the development of highly selective mitochondrial anti-tumor drugs. Moreover, the combination of TRAP1 inhibition and current traditional cancer therapies has shown promising applications. These findings have important implications for the diagnosis and treatment of tumors. Therefore, we reviewed the recently identified functions of the molecular chaperone TRAP1 in cancer development and progression, as well as the discovery and recent advances in selective TRAP1 inhibitors as anticancer drug therapies, opening up new attractive prospects for exploring strategies for targeting TRAP1 as a tumor cell target.

Exosomal microRNAs-mediated intercellular communication and exosome-based cancer treatment.

Exosomes are extracellular vesicles with a diameter of about 30 to 100 nm, which play a crucial role in intercellular communication. Compared with normal cells, the release rate of tumor-derived exosomes (TDEs) significantly increased, and exosomal contents, especially microRNAs (miRNAs), greatly changed. TDEs contribute to the proliferation, metastasis and resistance of tumor cells, regulate immune response and tumor autophagy, and mediate tumor-stroma communication. In addition, exosomes may be involved in tumor complications. In view of the role of exosomes in intercellular communication, exosomes have been developed as tumor biomarkers, therapeutic targets, and drug delivery systems for tumor diagnosis, prognosis and treatment. Despite the many advantages of exosomes, there are many challenges in exosomal development and application, such as incomprehensive understanding of biological functions, safety and specificity for therapeutic use. This article reviews the biogenesis of TDEs and focuses on the role of exosomal miRNAs in intercellular communication and exosome-based treatment for cancer.

Roles of galectin-3 in metabolic disorders and tumor cell metabolism.

The galactoside-binding protein galectin-3 is commonly overexpressed by cancer cells and promotes cancer progression and metastasis. Over the past few years, evidence has emerged that galectin-3 is also overexpressed in several metabolic malfunction conditions such as diabetes, obesity and atherosclerosis and is involved in the regulation of the occurrence and development of these diseases. Recently, Galectin-3 expression is shown also to be associated with glycolysis and mitochondrial metabolism in tumors, and promotes tumor metabolic reprogramming for their adaption to the microenvironment stress imposed by oxygen and nutrients deprivation. This brief review summarizes the current understanding of the roles and actions of galectin-3 in these metabolic diseases and in tumor metabolism.

Pantoprazole pretreatment elevates sensitivity to vincristine in drug-resistant oral epidermoid carcinoma in vitro and in vivo.

Resistance to chemotherapeutic agents is a major cause of treatment failure in patients with oral cancer. Proton pump inhibitors (PPIs), essentially H+-K+-ATPase inhibitors which are currently used in the treatment of acid related diseases, have demonstrated promising antitumor and chemo-sensitizing efficacy. The main purpose of the present study was to investigate whether pantoprazole (PPZ, one of PPIs) could increase the sensitivity of chemoresistant oral epidermoid carcinoma cells (KB/V) to vincristine (VCR) and elucidate the underlying action mechanism. Results showed that combination treatment of PPZ and VCR synergistically inhibited the proliferation of KB/V cells in vitro and in vivo. Furthermore, administration of PPZ and VCR not only induce apoptosis and G2/M phase arrest in KB/V cells but also suppress the migration and invasion of KB/V cells. The mechanism underlying synergistic anti-tumor effect of PPZ and VCR was related to the inhibition of the function and expression of P-glycoprotein (P-gp) and the down-regulation of EGFR/MAPK and PI3K/Akt/mTOR signaling pathways in KB/V cells. Additionally, we observed that PPZ treatment induced an increase in lysosomal pH and inhibited the activity of lysosomal enzyme acid phosphatase in KB/V cells, which could functionally reduce the sequestration of VCR in lysosomes and sensitized KB/V cells to VCR. In conclusion, our study demonstrated that PPZ could be included in new combined therapy of human oral cancer (especially on VCR-resistant therapy) together with VCR.