Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.
Neoplasms , Synthetic Lethal Mutations , Cell Death , DNA Repair , Neoplasms/drug therapy , Neoplasms/genetics
OBJECTIVE: This article aims to evaluate the survival benefits of simple cholecystectomy, extended cholecystectomy, as well as scope regional lymphadenectomy for T2 gallbladder cancer (GBC) patients. METHODS: We identified eligible patients from the Surveillance, Epidemiology, and End Results database. The confounding factors were controlled via propensity score matching. The log-rank test was utilized to compare overall survival. The multivariate Cox regression was then used to determine risk factors. RESULTS: Overall, data from 1,009 patients were obtained. The median overall survival (OS) of 915 patients that underwent simple cholecystectomy was 15 months; the median OS of 94 patients that underwent extended cholecystectomy was 17 months. There were no significant differences before and after propensity score matching (p = 0.542 and p = 0.258). The patients who received regional lymphadenectomy did show significant survival benefit, compared to those who did not receive regional lymphadenectomy. Furthermore, this benefit is observed in the N0 stage, but not observed in the N1 stage. In addition, the OS of patients who received lymphadenectomy for four or more regions was significantly better than those who received one to three regions lymphadenectomy. Age, the scope of regional lymphadenectomy, N stage, and tumor size were identified as prognostic factors. CONCLUSIONS: Extended cholecystectomy was not observed to significantly improve postoperative prognosis of patients with T2 GBC. However, there was a significant survival benefit shown for those with regional lymphadenectomy, particularly for patients with negative lymph nodes. Future studies on the control of potential confounding factors and longer follow-ups are still needed.
INTRODUCTION: Hepatocellular carcinoma (HCC) is a liver cancer with a poor prognosis. Owing to the complexity and limited pathogenic mechanism research on HCC, the molecular targeted therapy has been hindered. METHODS: In this study, we categorized transcriptome data into low-Myc and high-Myc expression groups in 365 HCC samples, screened the differentially expressed RNAs, including 441 DE-lncRNAs, 99 DE-miRNAs and 612 DE-mRNAs, constructed a lncRNA-miRNA-mRNA regulatory network, and selected a hub triple regulatory network through cytoHubba analysis. Through Gene ontology and KEGG pathway, a hub regulatory network was particularly enriched in the "Wnt signaling pathway" and "Cytochrome P450-arranged by substrate type" by Metascape. The prognostic genes in the hub regulatory network were evaluated by the RNA expression analysis, Kaplan-Meier (KM) survival analysis, and correlation analysis. RESULTS: The results showed that miR-212-3p/SLC6A1 axis was a potential prognostic model for HCC. Furthermore, IHC analysis showed down-regulated expression of SLC6A1 in HCC tissues and Alb-Cre;Myc mouse liver cancer tissues. The genetics and epigenetic analysis indicated that SLC6A1 expression was negatively correlated with DNA methylation. Immune infiltration analysis showed a negative relation between SLC6A1 and T cell exhaustion/monocyte in liver cancer tissues. CONCLUSION: In summary, the study revealed that miR-212-3p/SLC6A1 axis could serve as a crucial therapeutic target for HCC.
