文章：

多发性骨髓瘤中靶向Pim激酶的研究

Targeting the Pim kinases in multiple myeloma

原文发布日期：2015-07-17

DOI: 10.1038/bcj.2015.46

类型: Review

开放获取: 是

英文摘要：

Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM.

摘要翻译： 

多发性骨髓瘤（MM）是一种目前仍无法治愈的浆细胞恶性肿瘤，亟需能改善生存的新型治疗策略。Pim激酶是一个丝氨酸/苏氨酸激酶小家族，在血液系统恶性肿瘤中普遍呈现高表达。其中Pim-2在多发性骨髓瘤中表达最高，成为颇具前景的治疗靶点。它经骨髓微环境上调后介导肿瘤增殖并促进多发性骨髓瘤存活。Pim-2在典型的多发性骨髓瘤骨破坏中也发挥关键作用。Pim激酶在多发性骨髓瘤中的其他推定功能包括恶性细胞运输、促进缺氧骨髓微环境中的致癌信号传导以及介导治疗耐药性。目前已有多种Pim抑制剂处于研发阶段，先导化合物正进入临床试验。近期研究表明ATP竞争性Pim抑制剂LGH447在多发性骨髓瘤中具有单药活性。预计抑制Pim激酶与标准治疗和/或靶向多发性骨髓瘤其他生存通路的新型药物联合使用，将带来临床获益。

原文链接：

Targeting the Pim kinases in multiple myeloma