Background and objective
The tumor microenvironment and tumor immunity are crucially involved in tumor therapy. Immune checkpoint inhibitors targeting PD‐1/PD‐L1 signal transduction have been widely used in tumor therapy and have shown ideal clinical efficacy. However, some kinds of cancers still do not respond to PD‐1/PD‐L1 blockade therapy effectively, including gastric cancer. The related factors should be explored.
Methods and results
This review summarizes the recent progression of understanding the influence of Helicobacter pylori infection on PD‐1/PD‐L1 blockade therapy. Current pieces of evidence have indicated that H. pylori infection might affect the curative effect of tumor therapy associating with the induced immunomodulation.
Conclusion
It is necessary to understand the overall integration of PD‐1/PD‐L1 blockade therapy, the tumor microenvironment, and H. pylori infection. Much attention on the influence of H. pylori infection on the efficacy of tumor immunotherapy should be paid.
Maternal embryonic leucine zipper kinase (MELK) is known to modulate intracellular signaling and control cellular processes. However, the role of MELK in oncogenesis is not well defined. In this study, using two microarray datasets of neuroblastoma (NB) patients, we identified that MELK expression is significantly correlated to poor overall survival, unfavorable prognosis, and high-risk status. We found that MELK is a direct transcription target of MYCN and MYC in NB, and MYCN increases MELK expression via direct promoter binding. Interestingly, knockdown of MELK expression significantly reduced the phosphorylation of target protein Retinoblastoma (pRb) and inhibited NB cell growth. Furthermore, pharmacological inhibition of MELK activity by small-molecule inhibitor OTSSP167 significantly inhibited cell proliferation, anchorage-independent colony formation, blocked cell cycle progression, and induced apoptosis in different NB cell lines including a drug-resistant cell line. Additionally, OTSSP167 suppressed NB tumor growth in an orthotopic xenograft mouse model. Overall, our data suggest that MELK is a novel therapeutic target for NB and its inhibitor OTSSP167 is a promising drug for further clinical development.
MET amplification is a rare incidence in TNBCs. cMET overexpression is infrequent in TNBCs and may not be driven by gene amplification. Neither have significant prognostic value nor do they correlate with other clinicopathological characteristics in this TNBC cohort.
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