SPOP: new treatment target for renal cancer

In recent years, the incidence of renal cancer increased the rate of malignant tumors in the first place. Clinical treatment shows that renal cancer is not sensitive to radiotherapy and chemotherapy. VEGFR inhibitors such as sorafenib and sunitinib are the first-line drugs for advanced renal cell carcinoma. Although FDA-approved drugs for kidney cancer treatment has been up to ten, these drugs are very limited efficacy of metastatic renal cell carcinoma, and susceptible to drug resistance. According to previous research using recombinant mouse proteins, it is a very important and urgent task to discover and confirm the new drug targets for the treatment of RCC-specifics.

Liu Jiang, a researcher at the Beijing Genomics Institute of the Chinese Academy of Sciences, discovered early that the SPP of the ubiquitin ligase E3 family member Cul3-binding substrate protein was overexpressed in 99% of clear-cell renal cell carcinoma tissues and was expressed in normal renal tissue SPOP and is still a biomarker of clear cell renal cell carcinoma. SPOP is still overexpressed in metastatic clear cell renal carcinoma. Liu Jiang group further study showed that SPOP is incorrectly positioned in the cytoplasm cell renal cell carcinoma. Overexpression of hypoxia-inducible factor HIF transcription enhances SPOP overexpression and hypoxic microenvironment drives the accumulation of overexpressed SPOP proteins in the cytoplasm of renal carcinoma and ultimately promotes the formation of renal carcinoma.

The above fundamental research in biology poses a key scientific question whether small molecule compounds can targetly interfere with SPOP-mediated protein interactions to achieve specific treatment of clear cell renal cell carcinoma. In order to study the interaction between SPOP and protein, SPROP was used to identify the crystal structure of the substrate polypeptide complex, and the structure-based screening strategy was used in combination with drug Chemical synthesis optimization and other technical means. The successful acquisition of SPOP can be combined with small molecule compounds. The compound can inhibit the binding of SPOP to substrate protein, interfering with the SPOP-mediated regulation of ubiquitination of PTEN, DUSP7 and other ubiquitination-modified signal transduction pathway, and ultimately inhibiting the growth of clear cell renal carcinoma cells in vitro and in vivo. This important result is published in the journal Cancer Cell. This study provides evidence for the pharmacological function of SPOP as a target for clear-cell renal cell carcinoma, as well as a new direction for the discovery of SPOP inhibitors and for the treatment of renal cell carcinoma, unlike kinase inhibitors. Almost at the same time, Nature has published two reports on the hypoxia-inducible factor HIF-2α inhibitor PT2399 (analogue PT2385 has entered the clinical stage), suggesting that the HIF pathway for the Small molecule inhibitors will also become a new target for renal cancer treatment. Flarebio offers recombinant proteins of good quality such as recombinant Itgb2 for your research.