多发性骨肉瘤的治疗前景之一：CAR-T技术

icartab

Promising therapies in multiple myeloma

Progress in medical research has enhanced our understanding of tumor biology, delineated genetic and molecular mechanisms of tumor growth and survival, and defined the impact of the microenvironment in cancer pathogenesis. As a consequence of these advances, cancers deemed rapidly fatal only a few decades ago can now be treated effectively, with prolonged survival in an increasing proportion of patients. This is particularly true for multiple myeloma (MM), in which the introduction of drugs targeting the tumor in its microenvironment, such as the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, into initial, consolidation, maintenance, and salvage therapies hasmarkedly improved patient outcome. In this perspective, we discuss the most promising therapies to even further improve MM treatment, with a focus on drugs inhibiting the ubiquitin-proteasome pathway; histone deacetylase (HDAC) inhibitors (HDACIs); immune therapies including IMiDs, monoclonal antibodies (mAbs), immune checkpoint inhibitors, agents targeting accessory plasmacytoid dendritic cells (pDCs), vaccines, and chimeric antigen receptor–engineered T (CAR-T) cells; drugs targeting tumor cell homing to, and exploiting hypoxia in, the bonemarrow (BM) microenvironment; molecularly targeted therapies against kinesin spindle protein (KSP), v-aktmurine thymoma viral oncogene homolog 1 (AKT), exportin 1 (XPO1), cyclin-dependent kinases (CDKs), bromodomain and extraterminal (BET) bromodomain 4, and serine/ threonine kinase 4 (STK4); as well as delineating the impact of genomics on MM therapy. These advances in understanding the biology of MM will allow for earlier treatment of patients using rationally informed combination therapies with curative potential.

多发性骨肉瘤的治疗前景之一：CAR-T技术

随着医学研究的进展，提高了我们对肿瘤生物学的认识，明确了肿瘤生长和生存的基因和分子机制，并确定了微环境在肿瘤发病中的作用。由于这些进展的结果，癌症通常被认为是致命的，只在几十年前开始，癌症才可以有效地进行治疗，在不断增加的癌症病人中延长生存时间。这种情况对于多发性骨肉瘤尤其如此，对肿瘤微环境的靶向治疗药物的引入，如蛋白酶体抑制剂硼替佐米和免疫调节药物（IMiDs）沙利度胺及来那度胺，使得患者在初始，巩固，维护，和抢救治疗阶段有着显著的改善。从这个角度来，我们讨论最有前途进一步治疗MM的方法，焦点集中在抑制泛素-蛋白酶体途径的药物；组蛋白去乙酰化酶（HDAC）抑制剂（HDACis）；免疫治疗包括免疫调节药、单克隆抗体（mAb）、免疫检查点抑制剂、靶向药物辅助的浆细胞样树突状细胞（pDCs）、疫苗和嵌合抗原受体–T（CAR-T）细胞；靶向肿瘤细胞缺氧、骨髓（BM）微环境的药物···，以及使用规划MM治疗的基因组学。这些治疗进展增加了对MM生物学的理解，使得我们允许使用合理的组合疗法治疗患者。

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