Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

The development of cancers research based on mitochondrial heat shock protein 90.

Mitochondrial heat shock protein 90 (mtHsp90), including Tumor necrosis factor receptor-associated protein 1 (TRAP1) and Hsp90 translocated from cytoplasm, modulating cellular metabolism and signaling pathways by altering the conformation, activity, and stability of numerous client proteins, and is highly expressed in tumors. mtHsp90 inhibition results in the destabilization and eventual degradation of its client proteins, leading to interference with various tumor-related pathways and efficient control of cancer cell development. Among these compounds, gamitrinib, a specific mtHsp90 inhibitor, has demonstrated its safety and efficacy in several preclinical investigations and is currently undergoing evaluation in clinical trials. This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.

Demonstration of the impact of COVID-19 on metabolic associated fatty liver disease by bioinformatics and system biology approach.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) has caused a great threat to human health. Metabolic associated fatty liver disease (MAFLD) is a liver disease with a high prevalence rate. Previous studies indicated that MAFLD led to increased mortality and severe case rates of COVID-19 patients, but its mechanism remains unclear. METHODS: This study analyzed the transcriptional profiles of COVID-19 and MAFLD patients and their respective healthy controls from the perspectives of bioinformatics and systems biology to explore the underlying molecular mechanisms between the 2 diseases. Specifically, gene expression profiles of COVID-19 and MAFLD patients were acquired from the gene expression omnibus datasets and screened shared differentially expressed genes (DEGs). Gene ontology and pathway function enrichment analysis were performed for common DEGs to reveal the regulatory relationship between the 2 diseases. Besides, the hub genes were extracted by constructing a protein-protein interaction network of shared DEGs. Based on these hub genes, we conducted regulatory network analysis of microRNA/transcription factors-genes and gene - disease relationship and predicted potential drugs for the treatment of COVID-19 and MAFLD. RESULTS: A total of 3734 and 589 DEGs were screened from the transcriptome data of MAFLD (GSE183229) and COVID-19 (GSE196822), respectively, and 80 common DEGs were identified between COVID-19 and MAFLD. Functional enrichment analysis revealed that the shared DEGs were involved in inflammatory reaction, immune response and metabolic regulation. In addition, 10 hub genes including SERPINE1, IL1RN, THBS1, TNFAIP6, GADD45B, TNFRSF12A, PLA2G7, PTGES, PTX3 and GADD45G were identified. From the interaction network analysis, 41 transcription factors and 151 micro-RNAs were found to be the regulatory signals. Some mental, Inflammatory, liver diseases were found to be most related with the hub genes. Importantly, parthenolide, luteolin, apigenin and MS-275 have shown possibility as therapeutic agents against COVID-19 and MAFLD. CONCLUSION: This study reveals the potential common pathogenesis between MAFLD and COVID-19, providing novel clues for future research and treatment of MAFLD and severe acute respiratory syndrome coronavirus 2 infection.