Fig. 2

Cytokine signaling in lung cancer and coronavirus disease 2019 (COVID-19). Interleukin (IL)-6 accumulates as a result of nuclear factor (NF)-κB activation or stimulation by other cytokines, such as tumor necrosis factor (TNF)-α. The accumulated IL-6 plays a key role in a systemic hyperactivated immune response known as the cytokine storm. IL-6 serves as a driver of tumor progression, and several cancer-related risk factors may in turn boost IL-6 expression, driving the unfavorable cytokine storm. Furthermore, cytokine overproduction exacerbates COVID-19, and elevated IL-6 levels have been observed in patients with severe COVID-19. IL-6-mediated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is initiated by the binding of IL-6 to the IL-6 receptor (IL-6R) and subsequent interaction with gp130. The IL-6/IL-6R/gp130 complex, then, activates JAK enzymes, which phosphorylate gp130, providing docking sites for STAT3. JAK, then, phosphorylates STAT3 and subsequently induces the transcription of multiple target genes. XPO1 inhibitors such as selinexor and verdinexor abolish XPO1-mediated IκB export, thus reducing NF-κB pathway and decreasing the production of proinflammatory cytokines. Bruton tyrosine kinase (BTK) inhibitors inhibit NF-κB signaling, resulting in reduced IL-6 production. Corticosteroids inhibit TNF-α-mediated IL-6 mRNA expression. Other targeted therapeutics for the treatment of cancer and COVID-19, such as IL-6R antibodies and JAK inhibitors, are shown