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In addition, the increase in proinflammatory cytokines leads to the formation of fibrin amyloid microclot resistant to fibrinolysis, either by increased production of serum amyloid A (SAA) or by the release of -amyloid (A) peptide by platelets, resulting in capillary obstruction (156159)

At some point, elevated ROS production will reach a level where A production increases due to -secretase and ?-secretase activation

"Entombed A.D

Yoon et al., 2014

Based on this information in addition to our findings, we hypothesize that the combination of metformin and cytotoxic therapy may increase the therapeutic efficacy primarily in ASCL1-expressing SCLCs