Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia

Journal of Hematology & Oncology
Pei-Jie ShiJian-Pei Fang

Abstract

Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR) inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK) down-regulation in the treatment of ALL. The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model. When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 ...Continue Reading

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Citations

Feb 24, 2019·Cells·Carolina SimioniLuca M Neri
Dec 4, 2020·International Journal of Molecular Sciences·Janine Wörthmüller, Curzio Rüegg

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Methods Mentioned

BETA
PCR
transfection
electrophoresis
flow cytometry

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