INTRODUCTION
tumor, aggressive hematological malignancy, ALL
PROLIFERATION, TUMOR, ACUTE LYMPHOBLASTIC LEUKEMIA
Acute lymphoblastic leukemia (ALL) is an aggressive hematological malignancy. Despite the use of intensive multi‐agent chemotherapy regimens, relapse is common, particularly in older adults.The rationale for targeting mTOR in ALL comes from previous studies of the effects of mTOR inhibitors on lymphoid cells. The natural product sirolimus (rapamycin) and its derivatives, which were the first identified mTOR inhibitors, not only modulate proliferation of normal T cells,Sapanisertib (TAK‐228, MLN0128) is an orally bioavailable dual TORC1/TORC2 inhibitor that inhibits proliferation of a wide range of tumor cell lines.In light of these preclinical and clinical results, we conducted an open–label, multi‐institution Phase 2 study of single‐agent sapanisertib in patients with relapsed/refractory ALL that included measurement of plasma sapanisertib levels as well as serial analysis of bone marrow samples to assess target pathway inhibition.