Efficacy and safety of PD-1 inhibitors in recurrent or metastatic nasopharyngeal carcinoma patients after failure of platinum-containing regimens: a systematic review and meta-analysis.

OBJECTIVE: There is a lack of standard salvage treatment options for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that has failed platinum-containing regimens. Breakthroughs in immunotherapy have opened up new options for these patients. However, the efficacy and safety of immunotherapy have not been clarified. This study aimed to summarize and assess the efficacy and safety of PD-1 inhibitors in patients with RM-NPC who failed platinum-containing chemotherapy. METHODS: Up to August 25, 2022, clinical trials of PD-1 inhibitors in RM-NPC patients who failed platinum-containing regimens were searched in the PubMed, Embase, Cochrane, and Web of Science databases. Retrieval subject terms included "nasopharyngeal carcinoma", "metastatic", "recurrence", "PD-1", and "PD-L1". The clinical trials eligible for inclusion were systematically reviewed and meta-analyzed. RESULTS: A total of 9 studies including 842 patients with RM-NPC were included in this meta-analysis. The results showed that PD-1 inhibitors had promising efficacy in patients with RM-NPC who failed platinum-containing regimens: objective response rate (ORR) was 24% (95% confidence interval [CI] 21-26%), disease control rate (DCR) was 52% (95% CI 45-58%), 1-year progression-free survival (PFS) rate was 25% (95% CI 18-32%), and 1-year overall survival (OS) rate was 53% (95% CI 37-68%). In terms of treatment-related adverse events (AEs), the incidence of grade ≥ 3 treatment-related AEs was 19% (95% CI 13-24%). In addition, we found that PD-1 inhibitors were more effective in patients with PD-L1 positive than in patients with PD-L1 negative nasopharyngeal carcinoma who had failed platinum-containing regimens (ORR 31% (95%CI 26-35%) vs. 21% (95% CI 17-25%)). CONCLUSION: PD-1 inhibitors may provide a survival benefit for patients with RM-NPC who have failed platinum-containing regimens and have the advantage of a good safety profile, making them a promising treatment option.

Investigation of Hippo pathway-related prognostic lncRNAs and molecular subtypes in liver hepatocellular carcinoma.

This study aimed to investigate Hippo pathway-related prognostic long noncoding RNAs (lncRNAs) and their prognostic value in liver hepatocellular carcinoma (LIHC). Expression and clinical data regarding LIHC were acquired from The Cancer Genome Atlas and European Bioinformatics Institute array databases. Hippo pathway-related lncRNAs and their prognostic value were revealed, followed by molecular subtype investigations. Differences in survival, clinical characteristics, immune cell infiltration, and checkpoint expression between the subtypes were explored. LASSO regression was used to determine the most valuable prognostic lncRNAs, followed by the establishment of a prognostic model. Survival and differential expression analyses were conducted between two groups (high- and low-risk). A total of 313 Hippo pathway-related lncRNAs were identified from LIHC, of which 88 were associated with prognosis, and two molecular subtypes were identified based on their expression patterns. These two subtypes showed significant differences in overall survival, pathological stage and grade, vascular invasion, infiltration abundance of seven immune cells, and expression of several checkpoints, such as CTLA-4 and PD-1/L1 (P < 0.05). LASSO regression identified the six most valuable independent prognostic lncRNAs for establishing a prognosis risk model. Risk scores calculated by the risk model assigned patients into two risk groups with an AUC of 0.913 and 0.731, respectively, indicating that the high-risk group had poor survival. The risk score had an independent prognostic value with an HR of 2.198. In total, 3007 genes were dysregulated between the two risk groups, and the expression of most genes was elevated in the high-risk group, involving the cell cycle and pathways in cancers. Hippo pathway-related lncRNAs could stratify patients for personalized treatment and predict the prognosis of patients with LIHC.

Tanshinone IIA derivatives induced S-phase arrest through stabilizing c-myc G-quadruplex DNA to regulate ROS-mediated PI3K/Akt/mTOR pathway.

Herein, a derivate from tanshinone IIA, 1,6,6-trimethyl-11-phenyl-7,8,9,10-tetrahydro-6H-furo[2',3':1,2]phenanthro[3,4-d]imidazole (TA25), has been synthesized and investigated as potential inhibitor against the proliferation, migration and invasion of lung cancer cells. MTT assay and cell colony formation assay results showed that TA25 exhibits acceptable inhibitory effect against the proliferation of lung cancer A549 cells, and the value of IC50 was about 17.9 µM. This result was further confirmed by the inhibition of TA25 against the growth of xenograft lung cancer cells on zebrafish bearing tumor (A549 lung cancer cells). The results of wound-healing assay and FITC-gelatin invasion assay displayed that TA25 could inhibit the migration and invasion of lung cancer A549 cells. Moreover, the studies on the binding properties of TA25 interact with c-myc G-quadruplex DNA suggested that TA25 can bind in the G-quarter plane formed from G7, G11, G16 and G20 with c-myc G-quadruplex DNA through π-π stacking. Further study of the potential anti-cancer mechanism indicated that TA25 can induce S-phase arrest in lung cancer A549 cells, and this phenomenon resulted from the promotion of the production of reactive oxygen species and DNA damage in A549 cells under the action of TA25. Further research revealed that TA25 could inhibit the PI3K/Akt/mTOR signal pathway and increase the expression of p53 protein. Overall, TA25 can be developed into a promising inhibitor against the proliferation, migration and invasion of lung cancer cells and has potential clinical application in the near future.