Possible mechanisms of action of clarithromycin and its clinical application as a repurposing drug for treating multiple myeloma

Clarithromycin (CAM), a semisynthetic macrolide antibiotic, is a widely used antibacterial drug Recently, the efficacy of CAM as an add-on drug for treating multiple myeloma (MM) has been noted Its effect on treating MM has been confirmed in combination chemotherapies that include CAM However, a single treatment of CAM has no efficacy for treating MM Many myeloma growth factors (MGFs) including interleukin (IL)-6 are known to be closely involved in the development of MM CAM has been shown to suppress many MGFs, particularly IL-6 The possible mechanisms of action of CAM in treating MM have been suggested to include its immunomodulatory effect, autophagy inhibition, reversibility of drug resistance, steroid-sparing/enhancing effect and suppression of MGFs In addition, MM is characterised by uncontrolled cell growth of monoclonal immunoglobulin (Ig)-producing neoplastic plasma cells Large quantities of unfolded or misfolded Ig production may trigger considerable endoplasmic reticulum stress Thus, MM is originally a fragile neoplasm particularly susceptible to autophagy-, proteasomeand histone deacetylase 6-inhibitors Taken together, CAM plays an important role in MM treatments through its synergistic mechanisms In addition, CAM with its pleiotropic effects on cytokines including IL-6 and indirect antiviral effects might be worth a try for treating COVID-19