靶向骨髓微环境。

Targeting the Bone Marrow Microenvironment.

作者信息

Moschetta Michele, Kawano Yawara, Podar Klaus

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Department of Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany.

出版信息

Cancer Treat Res. 2016;169:63-102. doi: 10.1007/978-3-319-40320-5_6.

DOI:10.1007/978-3-319-40320-5_6

PMID:27696259

Abstract

Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years are predominantly based on our increasing understanding of the pathophysiologic role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms, which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing translational research aims to understand in more detail how disordered BM-niche functions contribute to MM pathogenesis and to identify additional derived targeting agents. One of the most exciting advances in the field of MM treatment is the emergence of immune therapies including elotuzumab, daratumumab, the immune checkpoint inhibitors, Bispecific T-cell engagers (BiTes), and Chimeric antigen receptor (CAR)-T cells. This chapter will review our knowledge on the pathophysiology of the BM microenvironment and discuss derived novel agents that hold promise to further improve outcome in MM.

摘要

在过去15年中，多发性骨髓瘤（MM）治疗取得了前所未有的进展，这主要基于我们对骨髓（BM）微环境病理生理作用的深入理解。事实上，包含沙利度胺、免疫调节药物（IMiDs）和蛋白酶体抑制剂的新治疗模式，既针对肿瘤细胞，也针对其BM微环境。正在进行的转化研究旨在更详细地了解紊乱的BM龛功能如何促进MM发病机制，并确定更多衍生的靶向药物。MM治疗领域最令人兴奋的进展之一是免疫疗法的出现，包括埃罗妥珠单抗、达雷妥尤单抗、免疫检查点抑制剂、双特异性T细胞衔接器（BiTes）和嵌合抗原受体（CAR）-T细胞。本章将回顾我们对BM微环境病理生理学的认识，并讨论有望进一步改善MM治疗结果的新型衍生药物。