Targeting the untargetable KRAS in cancer therapy

is one of the most well-known proto-oncogenes. Its gain-of-function mutations occur in approximately 30% of all human cancers. As the most frequently mutated isoform, KRAS is intensively studied in the past years. Despite its well-recognized importance in cancer malignancy, continuous efforts in the past three decades failed to develop approved therapies for mutant cancer. KRAS has thus long been considered to be undruggable. Encouragingly, recent studies have aroused renewed interest in the development of KRAS inhibitors either directly towards mutant KRAS or against the crucial steps required for KRAS activation. This review summarizes the most recent progress in the exploration of KRAS-targeted anticancer strategies and hopefully provides useful insights for the field.

Influence of Chemotherapy Combined with Thymopetidum on Cellular Immunity of Patients with Gastrointestinal Malignant Tumor in the Later Stage / 药物流行病学杂志

Objective:To study the infuence of chemotherapy combined with thymopetidum on cellular immunity of the patients with late gastrointestinal malignant tumor.Method:80 cases in the present study were divided into two groups:treatment group(40 cases treated by thymopetidum and chemotherapy) and controlled group(40 cases treated by chemotherapy only).25 cases without malignant tumors were grouped as a normal group.The activity of T-lymphocyte subgroup and its cytokines as IL-2(Th_1 ) and IL-10(Th2) in the peripheral blood of the treatment group were investigated before the treatment and on the tenth day after the treatment for two cycles.A statistical study was done between the two groups.Result:Before the treatment,T-lymphocyte subset(CD_3~+.CD_4~+ and the ratio of CD_4~+/CD_8~+ ) and IL-2 of the patients with gatrointestinal malignant tumor were lower than those of the normal group.The values of CD_8~+ and IL-10 were obviously increased,compared with those of the normal group.After the treatment for two cycles,CD_3~+,CD_4~+ and the ratio of CD_4~+ /CD_8~+ were higher respectively than those before the treatment in the two groups,and the changes in the tested group were higher than those in the controlled group.IL-2 of the tested group was lower respectively and its IL-10 was higher than before the treatment,but there was no significant difference for the controlled group.The efficiency of the tested group was higher than that of the controlled group.Conclusion:The immunity of T-lymphocyte subgroup was suppressed in the patients with gastrointestinal malignant tumor and the expression of Th2 type cytokines was enhanced.The cellular immunity of patients was improved by killing tumor cells and removing the immunosuppressive agents after the chemotherapy together with thymopetidum.