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In addition, life\u2010long irreversible late effects from chemo\u2010 and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3\u2010phosphate kinase (PI3K)\/Akt\/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug\u2010resistance of cancer cells, and it is frequently upregulated in the different subtypes of B\u2010ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B\u2010ALL patients. Promising preclinical data on PI3K\/Akt\/mTOR inhibitors have documented their anticancer activity in B\u2010ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event\u2010free survival and reduce therapy\u2010associated toxicity for patients with B\u2010ALL. This review highlights the current status of PI3K\/Akt\/mTOR inhibitors in B\u2010ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26539","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T06:38:04Z","timestamp":1524033484000},"page":"6440-6454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Targeting the phosphatidylinositol 3\u2010kinase\/Akt\/mechanistic target of rapamycin signaling pathway in B\u2010lineage acute lymphoblastic leukemia: An update"],"prefix":"10.1002","volume":"233","author":[{"given":"Carolina","family":"Simioni","sequence":"first","affiliation":[{"name":"Department of Morphology, Surgery and Experimental Medicine University of Ferrara  Ferrara 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