RPS6 and cancer: Upregulation of compensatory RAS effector pathways in response to mTOR inhibition occurs through a variety of mechanisms, including the upregulation of ERK or WNT signaling.8–11 These adaptive changes lead to sustained activation of key downstream targets such as p70-S6 kinase (p70S6K) or ribosomal protein S6 (RPS6), the activation of which can confer resistance to ERK pathway inhibitors.12,13 This observation has led to attempts to combine multiple RAS effector targeted therapies for GBM and other cancers.