...human T-ALL cell lines were treated in vitro with increasing concentrations of MRK-003 in the presence of 1 nM or 100 nM rapamycin...increasing amounts of GSI reduced human leukemic growth, however the addition of rapamycin enhanced the effects of GSI treatment, resulting in greater inhibition of growth...mice treated with GSI and rapamycin survived on average longer than vehicle-treated mice or mice treated with either single agent (GSI or rapamycin alone; Figure 7C). The administration of GSI and rapamycin resulted in an increase in the percentage of mice surviving (60% vs 25%) as well as an increase in the mean survival period of more than 50 days (P < .058 by log rank test)...Collectively, these in vivo data suggest that GSI in combination with the mTOR inhibitor rapamycin may have added efficacy in the treatment of T-ALL patients who exhibit NOTCH1 activation.