Renal cell carcinoma (RCC) is a tumor with unpredictable presentation and poor clinical outcome. RCC is always resistant to chemotherapy and radiation, and weakly sensitive to immunotherapeutic agents. Therefore, novel agents and approaches are urgently needed for the treatment of RCC. Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese herbs, has been implicated in a wide variety of pharmacological effects, such as anti‐inflammatory, antiviral, and antitumor activities. However, its role in RCC remains unknown. In this study, we found that emodin effectively killed renal cancer cells without significant toxicity to noncancerous cell HK‐2. Flow cytometry assay with Annexin V‐FITC and PI demonstrated that emodin induces necroptosis, but not apoptosis, in renal cancer cells. Meanwhile, the phosphorylation levels of RIP1 and MLKL, the key necroptosis‐related proteins, were significantly increased. To explore how emodin inhibits kidney tumor growth, we tested reactive oxygen species (ROS) levels and found that the levels of ROS increased upon emodin treatment in a dose‐dependent manner. Further studies demonstrated that emodin induces necroptosis through ROS‐mediated activation of JNK signaling pathway and also inhibits glycolysis by downregulation of GLUT1 through ROS‐mediated inactivation of the PI3K/AKT signaling pathway. Our findings revealed the potential mechanisms by which emodin suppresses renal cancer cell growth and will help develop novel therapeutic approaches for patients with JNK‐ or PI3K/AKT‐dysregulated renal cancer.

The receptor-interacting protein kinase 3 (RIP3/RIPK3) was recently found to be a critical regulator of programmed necrosis/necroptosis. However, the biological role and clinical significance of RIP3 in prostate cancer remain obscure. Western blotting and QRT-PCR were performed to detect the level of RIP3 in prostate cancer cells. Fixed cancer tissue and normal tissue specimens were subjected to immunohistochemical analysis of RIP3. Cell migration and invasion abilities were evaluated by transwell assays. In vitro proliferative ability was examed by MTS. And in vivo nude mice model were used to evaluate the effect of RIP3 ectopic expression on proliferative capability. Cell cycle of prostate cancer cells were analyzed by flow cytometry. Changes in some related proteins caused by RIP3 overexpression were explored using Western blotting. RIP3 was significantly down-regulated in prostate cancer cell lines and clinical prostate tumor samples. And over-expressing RIP3 suppressed the migration and invasion of prostate cancer cells. Two important matrix metalloproteinases MMP2, MMP9 which enables the destruction of the histological barrier of tumor cell invasion and three mesenchymal markers Vimentin, fibronectin, and N-cadherin were under-expressed due to the overexpression of RIP3, but the E-cadherin level which is the epithelial marker was increased. Furthermore, our results also showed that RIP3 can inhibit the proliferation and tumorigenicity of prostate cancer cells both in vitro and in vivo by phosphorylating MLKL, which were reversed by MLKL inhibitor treatment, indicating that necroptosis was involved in cell death. Taken together, these findings indicated that RIP3 is responsible for the progression of prostate cancer, suggesting that RIP3 might have the potential to be a prognostic marker or a therapeutic target against prostate cancer.

DUXAP10 is a member of long non-coding RNAs (lncRNAs) and has been reported to be upregulated in bladder cancer (BC) tissues. However, the biological functions of DUXAP10 in BC are largely unknown. The present study detected the expression of DUXAP10 in human normal bladder cell SV‑HUC‑1 and BC cell lines. Subsequently, cell proliferation, cell cycle, and apoptosis were analyzed by knockdown of the DUXAP10 expression. Results suggested that the expression level of DUXAP10 was significantly enhanced in cancer cells. After knockdown of DUXAP10, cell proliferation was inhibited, cell cycle was arrested at G0/G1 phase, and apoptosis was increased in T24 and 5637 cells. Western blot analysis detected that knockdown of DUXAP10 decreased the expression of Bcl-xL, cyclin D and CDK4. This increased the expression of Bad, cleaved caspase‑3, cleaved caspase-9, and p27. Further studies indicated that knockdown of DUXAP10 inhibited PI3K/Akt/mTOR signaling pathway. Combining these results, our study suggests that DUXAP10 plays an important role in BC and DUXAP10 inhibition is a potential therapeutic target for BC.

Treatment of urolithiasis depends on several important factors which include stone location, size, composition, and patient symptoms. Although significant advancements have been made in the surgical management of urolithiasis in the last decade, pharmacotherapy which can prevent the formation of new stones and decrease the recurrence of urolithiasis has not experienced the same level of success. Currently, urolithiasis is regarded as a complicated syndrome that is determined by numerous factors, and any treatment plan for urolithiasis should be individualized while considering any potential damage arising from stone-forming factors. This review introduces the most popular methods currently used to evaluate urolithiasis and the pharmacotherapy of urolithiasis based on patient-specific factors.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive variant of castration-resistant prostate cancer. It is characterized by low or no expression of the androgen receptor (AR), activation of AR-independent signaling, and increased neuroendocrine phenotype. Most of NEPC is induced by treatment of androgen deprivation therapy and androgen receptor pathway inhibitors (ARPIs). Currently, the treatment of NEPC follows the treatment strategy for small-cell lung cancer, lacking effective drugs and specific treatment options. This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (zeste homolog 2 inhibitors, lysine-specific demethylase 1 inhibitors), aurora kinase A inhibitors, poly-ADP-ribose polymerase inhibitors, delta-like ligand 3 targeted therapies, a combination of immunotherapies, etc. Other promising targets and future directions are also discussed in this review. These novel targets and therapies may provide new opportunities for the treatment of NEPC.