Overcoming drug resistance by targeting protein homeostasis in multiple myeloma.
Overcoming drug resistance by targeting protein homeostasis in multiple myeloma.
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DOI：
10.20517/cdr.2021.93
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Bianchi G
中科院分区：
文献类型：
--
作者：
Moscvin M;Ho M;Bianchi G
多发性骨髓瘤（MM）是一种浆细胞疾病，其典型特征是克隆性免疫球蛋白或游离轻链的大量合成。虽然无法治愈，但在过去二十年中，对MM病理生物学的深入了解推动了重大的治疗进展，显著改善了患者的预后。蛋白酶体抑制剂、免疫调节药物和单克隆抗体是最有效的抗mm药物，不仅针对癌细胞，而且针对骨髓微环境。然而，已经报道了从头耐药，随着时间的推移，获得性耐药对大多数患者来说是不可避免的，导致复发/难治性疾病和不良预后。持续的蛋白质合成加上受损/不足的蛋白质水解机制使MM细胞对蛋白质稳态的扰动非常敏感，为我们提供了靶向这种内在脆弱性的治疗目的的机会。这篇综述强调了临床使用fda批准的和研究性药物靶向MM蛋白稳态的科学依据。
Multiple myeloma (MM) is a plasma cell disorder typically characterized by abundant synthesis of clonal immunoglobulin or free light chains. Although incurable, a deeper understanding of MM pathobiology has fueled major therapeutical advances over the past two decades, significantly improving patient outcomes. Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies are among the most effective anti-MM drugs, targeting not only the cancerous cells, but also the bone marrow microenvironment. However, de novo resistance has been reported, and acquired resistance is inevitable for most patients over time, leading to relapsed/refractory disease and poor outcomes. Sustained protein synthesis coupled with impaired/insufficient proteolytic mechanisms makes MM cells exquisitely sensitive to perturbations in protein homeostasis, offering us the opportunity to target this intrinsic vulnerability for therapeutic purposes. This review highlights the scientific rationale for the clinical use of FDA-approved and investigational agents targeting protein homeostasis in MM.
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影响因子：
50.3
作者：
Anchoori RK;Karanam B;Peng S;Wang JW;Jiang R;Tanno T;Orlowski RZ;Matsui W;Zhao M;Rudek MA;Hung CF;Chen X;Walters KJ;Roden RB
通讯作者：
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影响因子：
3.7
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通讯作者：
Dillon N
DOI：
10.1083/jcb.137.4.825
发表时间：
1997-05-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Agarraberes FA;Terlecky SR;Dice JF
通讯作者：
Dice JF
影响因子：
--
作者：
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影响因子：
20.3
作者：
Catley, Laurence;Weisberg, Ellen;Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.