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Top I inhibition triggers autophagy via m-TOR suppression. Topoisomerase I inhibition by irinotecan or topotecan generates reactive oxygen species (ROS), which drives the activation of JNK/AMP and p38/MAPK. JNK phosphorylation activates SESN2, followed by AMPK. p38 activation via ROS upregulates MAPK. These two pathways converge on m-TOR, where m-TOR inhibition triggers autophagic flux.
