Programmed death 1 (PD-1) inhibitors have emerged as the new standard of care for the second-line treatment of advanced esophageal squamous cell carcinoma. There have been lots of research lately concerning the topic. A comprehensive assessment of the efficacy and safety profile between PD-1 inhibitors and chemotherapy is warranted. Hence, we carried out a systematic review and meta-analysis to illustrate this issue. Pubmed, Embase, Cochrane Library, and Embase were searched systematically until May 1, 2022. We extracted data on efficacy and safety and calculated the pooled hazard ratios (HRs) and relative ratios (RRs) with 95% CI using randomized-effect or fixed-effect models. A subgroup analysis was applied to explore the factors modifying the response to PD-1 inhibitors. Ultimately, a total of 5 studies involving 1970 patients were included in our meta-analysis. PD-1 inhibitors group could attain greater overall survival (OS) benefit (HR = 0.73, 95% CI: 0.66–0.81, P < 0.001) and nearly favorable progression-free survival (HR = 0.89, 0.76–1.04, P = 0.13). Treatment-related adverse events (RR = 0.76, 95% CI: 0.64–0.91, P = 0.004) and level 3–5 treatment-related adverse events (RR = 0.40, 95% CI: 0.32–0.49, P < 0.001) were significantly diminished in PD-1 inhibitors groups. Among all modifying factors, programmed death ligand 1 combined positive score was positively associated with the patient’s OS. The analysis suggests that PD-1 inhibitors exhibited better survival outcomes and safety profiles than standard-of-care chemotherapy. High levels of programmed death ligand 1 combined positive scores were associated with an enhanced response to PD-1 immunotherapies concerning OS.

With the advent of Kirsten rat sarcoma viral oncogene homologue G12C (KRAS G12C) inhibitors, RAS is no longer considered undruggable. For the suppression of RAS, new therapeutic approaches have been suggested. However, current clinical studies have indicated therapeutic resistance after short-lived tumour suppression. According to preclinical studies, this might be associated with acquired genetic alterations, reactivation of downstream pathways, and stimulation for upstream signalling. In this review, we aimed to summarize current approaches for combination therapy to alleviate resistance to KRAS G12C inhibitors in colorectal cancer with a focus on the mechanisms of therapeutic resistance. We also analysed the relationship between various mechanisms and therapeutic resistance.

Purpose: PD-1 inhibitors have emerged as the new standard of care for second-line treatment of advanced esophageal squamous cell carcinoma. There have been lots of research lately concerning the topic. A comprehensive assessment of the efficacy and safety profile between PD-1 inhibitors and chemotherapy is warranted. Methods: PubMed, Embase, Cochrane Library, and Embase were searched systematically until May 1st, 2022. We extracted data on efficacy and safety and calculated the pooled HRs and RRs with 95%CI using randomized-effect or fixed-effect models. A subgroup analysis was applied to explore the factors modifying the response to PD-1 inhibitors. All data were statistically analyzed by R 4.1.2. Results: A total of 5 studies involving 1,970 patients were included in our meta-analysis. PD-1 inhibitors group could attain greater overall survival benefit (HR = 0.73, 95%CI 0.66-0.81, P < 0.001) and nearly favorable progression-free survival (HR = 0.89, 0.76-1.04, P = 0.13). TRAEs (RR = 0.76, 95%CI 0.64-0.91, P = 0.004) and level 3-5 TRAEs (RR = 0.40, 95%CI 0.32-0.49, P < 0.001) were significantly diminished in PD-1 inhibitors groups. Among all modifying factors, PD-L1 combined positive score was positively associated with the patient’s overall survival. Conclusions: This analysis suggests that PD-1 inhibitors exhibited better survival outcomes and safety profiles than standard-of-care chemotherapy. High levels of PD-L1 combined positive scores was associated with an enhanced response to PD-1 immunotherapies with regard to overall survival.