Inhibition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in hematologic malignancies

被引：89

作者：

Witzig T.E. ^{[1
]}

Kaufmann S.H. ^{[1
]}

机构：

[1] Mayo Clinic, Rochester, MN 55905

来源：

Current Treatment Options in Oncology | 2006年 / 7卷 / 4期

关键词：

Rapamycin; Hematologic Malignancy; Everolimus; Mantle Cell Lymphoma; Acute Myelogenous Leukemia;

D O I：

10.1007/s11864-006-0038-1

中图分类号：

学科分类号：

摘要：

The phosphatidylinositol 3-kinase (PI3-K)/mammalian target of rapamycin (mTOR) signal transduction pathway integrates signals from multiple receptor tyrosine kinases to control cell proliferation and survival. Key components of the pathway are the lipid kinase PI3-K, the small guanosine triphosphate-binding protein Rheb, and the protein kinases Akt and mTOR. Important natural inhibitors of the pathway include the lipid phosphatase PTEN and the tuberous sclerosis complex. Several components of this pathway are targeted by investigational antineoplastic agents. Rapamycin (sirolimus), the prototypic mTOR inhibitor, exhibits activity in acute myeloid leukemia. Three rapamycin analogs, temsirolimus, everolimus, and AP23573, are in clinical trials for various hematologic malignancies. Temsirolimus has produced a 38% overall response rate in relapsed mantle cell lymphoma, and AP23573 has demonstrated activity in acute leukemia. Everolimus is undergoing clinical testing in lymphoma (Hodgkin and non-Hodgkin) and multiple myeloma. In addition, perifosine, an inhibitor of Akt activation that exhibits substantial antimyeloma activity in preclinical models, is being examined in relapsed multiple myeloma. Based on results obtained to date, it appears that inhibitors of the PI3-K/mTOR pathway hold promise as single agents and in combination for hematologic malignancies. Copyright © 2006 by Current Science Inc.

引用

页码：285 / 294

页数：9

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