To prevent and treat cancer cachexia with MEK inhibitor

Tumor cachexia is a multifactorial syndrome characterized by progressive skeletal muscle atrophy and weight loss, and this condition can’t be fully reversed by conventional nutritional support, leading to progressive organ dysfunction. Cachexia not only reduces the sensitivity of drug treatment and increases the incidence of complications, affecting the implementation of patients with comprehensive treatment programs, but also leads to decreased quality of life and survival of patients significantly to be reduced. Clinically, with the lack of cachexia drugs with effective prevention and treatment, new ideas based on the understanding of the new breakthrough of pathogenesis in the treatment of cachexia have been the hot spots in domestic and foreign research in recent years. More research through recombinant mouse proteins is needed.

Skeletal muscle atrophy is the most important clinical features of cachexia. Clinical and basic research has always been taking skeletal muscle atrophy as a prognostic indicator of clinical cancer patients with reduced quality of life and shortening life expectancy. When the weight of the cachexia was 30%, the reserve of skeletal muscle protein decreased by 75% and the survival time was significantly shortened. The journal Cell reported that the quality of animal skeletal muscle was not only able to effectively reverse the decline in cachexia and significantly prolong the survival of model animals without affecting the rate of tumor growth. These results suggest that slowing the cachexia skeletal muscle atrophy is an important goal of its prevention and treatment. But there is no clinical intervention in the current cachexia skeletal muscle atrophy drugs.

MEK / ERK signaling pathway is not only important in tumor cell proliferation and differentiation, but also in regulating skeletal muscle energy metabolism and protein synthesis. A clinical study of advanced cholangiocarcinoma showed that the specific adverse effect of the first generation MEK inhibitor siMedidine was an increase in skeletal muscle mass, but the mechanism was unknown. To this end, the animal experimental results of Dr. Yang Quanjun from Shanghai Jiaotong University Affiliated Sixth People's Hospital Guo Cheng Task Force showed that the preventive and therapeutic administration of sixtemidine can effectively prevent and interfere with tumor cachexia animal weight and skeletal muscle, and it also can reduce the expression of E3 ubiquitination ligase MuRF1 and MAFbx (skeletal muscle protein degradation mainly by the two ubiquitin ligated ligands) and reduce the food intake and serum cytokines. Further studies on MyHC and MEK / ERK-related signaling pathways in the gastrocnemius muscle showed that siemetilib could inhibit the activation of ERK and increase the phosphorylation of AKT, leading to a decrease in the phosphorylation of FoXO3α and GSK3β downstream and increase of phosphorylation of mTOR.

The results of the Gregory B. Lesinski team from the Winship Cancer Institute in Emory University show that the second-generation MEK inhibitor, Binimetinib, also increases skeletal muscle mass and the function is gained through promoting skeletal muscle fibers synthesis and inhibition of skeletal muscle protein ubiquitination degradation. These results suggest that antineoplastic MEK inhibitors may be used for the prophylaxis and treatment of certain advanced stages of the disease in the future. By the way, Flarebio provides you with superior recombinant proteins including recombinant ITGB5 at good prices.