The number of descriptions of emerging viruses has grown at an unprecedented rate since the beginning of the 21 st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is the third highly pathogenic coronavirus that has introduced itself into the human population in the current era, after SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Molecular and cellular studies of the pathogenesis of this novel coronavirus are still in the early stages of research; however, based on similarities of SARS-CoV-2 to other coronaviruses, it can be hypothesized that the NF-κB, cytokine regulation, ERK, and TNF-α signaling pathways are the likely causes of inflammation at the onset of COVID-19. Several drugs have been prescribed and used to alleviate the adverse effects of these inflammatory cellular signaling pathways, and these might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarize alterations of cellular signaling pathways that are associated with coronavirus infection, particularly SARS-CoV and MERS-CoV, and tabulate the therapeutic agents that are currently approved for treating other human diseases.

Genetic alterations, especially the K-Ras mutation, carry the heaviest burden in the progression of pancreatic precursor lesions into pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment is one of the challenges that hinder the therapeutic approaches from functioning sufficiently and leads to the immune evasion of pancreatic malignant cells. Mastering the mechanisms of these two hallmarks of PDAC can help us in dealing with the obstacles in the way of treatment. In this review, we have analyzed the signaling pathways involved in PDAC development and the immune system’s role in pancreatic cancer and immune checkpoint inhibition as next-generation therapeutic strategy. The direct targeting of the involved signaling molecules and the immune checkpoint molecules, along with a combination with conventional therapies, have reached the most promising results in pancreatic cancer treatment.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can substantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy.

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Patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, are at higher risk to develop colorectal cancer (CRC). However, the underlying mechanisms of this predisposition remain elusive. We performed in-depth comparative computational analyses to gain new insights, including weighted gene co-expression network analysis (WGCNA) and gene ontology and pathway enrichment analyses, using gene expression datasets from IBD and CRC patients. When individually comparing IBD and CRC to normal control samples, we identified clusters of highly correlated genes, differentially expressed genes, and module-trait associations specific for each disease. When comparing IBD to CRC, we identified common hub genes and commonly enriched pathways. Most notably, IBD and CRC share significantly increased expression of five genes (MMP10, LCN2, REG1A, REG3A, and DUOX2), enriched inflammatory and neutrophil activation pathways and, most notably, highly significant enrichment of IL-4 and IL-13 signaling. Thus, our work expands our knowledge about the intricate relationship between IBD and CRC development and provides new rationales for developing novel therapeutic strategies.