Here, we selectively disrupt the ability of rapidly proliferating cancer cells to spawn AKT1<sup>low</sup> daughter cells that are rare, slowly proliferating, tumor-initiating, and chemotherapy-resistant, using β1-integrin activation and the AKT1-E17K-mutant oncoprotein as experimental tools <i>in vivo</i> Surprisingly, we find that selective depletion of AKT1<sup>low</sup> slow proliferators actually reduces the growth of a molecularly diverse panel of human cancer cell xenograft models without globally altering cell proliferation or survival <i>in vivo</i> Moreover, we find that unusual cancer patients with AKT1-E17K-mutant solid tumors also fail to produce AKT1<sup>low</sup> quiescent cancer cells and that this correlates with significantly prolonged survival after adjuvant treatment compared with other patients.
Results In patients with AKT1 E17K-mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor-positive breast, gynecologic, and other solid tumors, respectively.