针对慢性髓性白血病肿瘤干细胞的新型治疗药物。
Novel therapeutic agents against cancer stem cells of chronic myeloid leukemia.
机构信息
Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
出版信息
Anticancer Agents Med Chem. 2010 Feb;10(2):111-5. doi: 10.2174/187152010790909326.
Abstract
Chronic myeloid leukemia (CML) is induced by the BCR-ABL oncogene, a product of Philadelphia (Ph) chromosome. The BCR-ABL kinase inhibitor imatinib is a standard treatment for Ph+ leukemia, and has been shown to induce a complete hematologic and cytogenetic response in most chronic phrase CML patients. However, imatinib does not cure CML, and one of the reasons is that imatinib does not kill leukemia stem cells (LSCs) in CML both in vitro and in vivo. Recently, several new targets or drugs have been reported to inhibit LSCs in cultured human CD34+ CML cells or in mouse model of BCR-ABL induced CML, including an Alox5 pathway inhibitor, Hsp90 inhibitors, omacetaxine, hedgehog inhibitor and BMS-214662. Specific targeting of LSCs but not normal stem cell is a correct strategy for developing new anti-cancer therapies in the future.
摘要
慢性髓性白血病（CML）是由 BCR-ABL 癌基因引起的，该基因是费城（Ph）染色体的产物。BCR-ABL 激酶抑制剂伊马替尼是 Ph+白血病的标准治疗方法，已证明它可诱导大多数慢性期 CML 患者的完全血液学和细胞遗传学反应。然而，伊马替尼并不能治愈 CML，其中一个原因是伊马替尼在体外和体内均不能杀死 CML 中的白血病干细胞（LSCs）。最近，据报道，几种新的靶点或药物可抑制培养的人 CD34+CML 细胞或 BCR-ABL 诱导的 CML 小鼠模型中的 LSCs，包括 Alox5 途径抑制剂、Hsp90 抑制剂、奥马曲星、 hedgehog 抑制剂和 BMS-214662。特异性靶向 LSCs 而不是正常干细胞是未来开发新抗癌疗法的正确策略。
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