GSTM5 and neoplasm: Ectopic expression of 3 of the most consistently upregulated genes involved in xenobiotic metabolism, Gstm1, Gstm3, and Gstm5, readily caused an increase in GST activity and resistance to sotorasib in PDX-dc1 and MIA Paca-2 human tumor cells known to be sensitive to sotorasib (30) (Figure 7, E and F, and Supplemental Figure 10), indicating that the GSTM class of detoxifying enzymes can modify the response to sotorasib, resulting in its reduced antitumor activity.