AKT1 and acute myeloid leukemia: These include PI3K/AKT, MEK/ERK, and JAK/STAT (Fig. 5).251 While targeting these signaling pathways has been an attractive strategy, unfortunately some phase I clinical trials showed that combined targeting of PI3K and MEK or mTOR signaling has little to no therapeutic window due to overwhelming toxicity prior to sufficient efficacy.266,267 Other mechanisms to inhibit c-Myc function in AML are being developed through suppression of c-Myc expression and activity.