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Background: Non-small cell lung cancers (NSCLC) harboring Human Epidermal Growth Factor Receptor 2 (HER2) mutations represent a distinct subset with unique therapeutic challenges. Although immune checkpoint inhibitors (ICIs) have been transformative in lung cancer treatment, the efficacy of ICIs in HER2-mutated NSCLC remains to be established. Methods: We systematically searched for real-world studies investigating the use of ICIs in treating HER2-mutated NSCLC, sourced from the PubMed, Cochrane Library, and Embase databases. Outcomes including objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were extracted for further analysis. Results: Twelve studies involving 260 patients were enrolled in this meta-analysis. Pooled data revealed an ORR of 0.26 (95% CI 0.17–0.34), a DCR of 0.68 (95% CI 0.55–0.81), and a median PFS (mPFS) of 5.36 months (95% CI 3.50–7.21). Notably, in the subgroup receiving combined immune and chemotherapy, the ORR increased to 0.37 (95% CI 0.26–0.49), the DCR to 0.79 (95% CI 0.70–0.87), and the mPFS to 7.10 months (95% CI 5.21–8.99). Conclusions: ICIs demonstrate promising anti-tumor activity and safety in patients with HER2-mutated NSCLC. Furthermore, the combined regimen of ICIs and chemotherapy may provide a significant therapeutic option for this patient population. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH), a common clinical disease, is becoming a leading cause of hepatocellular carcinoma (HCC). Dual specificity phosphatase 22 (DUSP22, also known as JKAP or JSP-1) expressed in numerous tissues plays essential biological functions in immune responses and tumor growth. However, the effects of DUSP22 on NASH still remain unknown. Here, we find a significant decrease of DUSP22 expression in human and murine fatty liver, which is mediated by reactive oxygen species (ROS) generation. Hepatic-specific DUSP22 deletion particularly exacerbates lipid deposition, inflammatory response and fibrosis in liver, facilitating NASH and non-alcoholic fatty liver disease (NAFLD)-associated HCC progression. In contrast, transgenic over-expression, lentivirus or adeno-associated virus (AAV)-mediated DUSP22 gene therapy substantially inhibit NASH-related phenotypes and HCC development in mice. We provide mechanistic evidence that DUSP22 directly interacts with focal adhesion kinase (FAK) and restrains its phosphorylation at Tyr397 (Y397) and Y576 + Y577 residues, subsequently prohibiting downstream activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) cascades. The binding of DUSP22 to FAK and the dephosphorylation of FAK are indispensable for DUSP22-meliorated NASH progression. Collectively, our findings identify DUSP22 as a key suppressor of NASH-HCC, and underscore the DUSP22-FAK axis as a promising therapeutic target for treatment of the disease. Mechanisms underlying the pathogenesis of nonalcoholic steatohepatitis are unclear. Here, the authors show that ROS-mediated DUSP22 degradation participates in the progression of fatty liver, contributing to the development of NASH and associated HCC via regulating FAK and its downstream ERK1/2 and NF-κB signaling cascade. [ABSTRACT FROM AUTHOR]