Department of Experimental Hematology, Medical University of Lodz, Lodz, Poland.
Department of Hematology, Medical University of Lodz, Ul. Ciolkowskiego 2, 93-510, Lodz, Poland.
Drugs R D. 2019 Jun;19(2):73-92. doi: 10.1007/s40268-019-0269-9.
Bortezomib is a dipeptidyl boronic acid that selectively inhibits the ubiquitin proteasome pathway, which plays a role in the degradation of many intracellular proteins. It is the first-in-class selective and reversible inhibitor of the 26S proteasome, with antiproliferative and antitumor activity. It exerts its anti-neoplastic action mainly via the inhibition of the nuclear factor-κB pathway components associated with cell proliferation, apoptosis, and angiogenesis. The drug has revolutionized the treatment of multiple myeloma and, more recently, mantle cell lymphoma. In 2003, bortezomib received accelerated approval from the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma and in 2008 for patients with previously untreated multiple myeloma. In 2006, bortezomib was approved for the treatment of refractory/relapsed mantle cell lymphoma and, in 2014, for previously untreated mantle cell lymphoma. Bortezomib has also demonstrated clinical efficacy both as a single drug and in combination with other agents in light chain amyloidosis, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, and peripheral T-cell lymphomas. Furthermore, continued clinical studies are required to confirm its value for patients with indolent and aggressive B-cell non-Hodgkin lymphomas and acute leukemias.
硼替佐米是一种二肽硼酸，选择性抑制泛素蛋白酶体途径，该途径在许多细胞内蛋白质的降解中起作用。它是 26S 蛋白酶体的首个选择性和可逆抑制剂，具有抗增殖和抗肿瘤活性。它主要通过抑制与细胞增殖、凋亡和血管生成相关的核因子-κB 途径成分发挥抗肿瘤作用。该药物彻底改变了多发性骨髓瘤的治疗方法，最近也改变了套细胞淋巴瘤的治疗方法。2003 年，硼替佐米获得美国食品和药物管理局加速批准，用于治疗复发性/难治性多发性骨髓瘤，2008 年用于未经治疗的多发性骨髓瘤患者。2006 年，硼替佐米被批准用于治疗难治性/复发性套细胞淋巴瘤，2014 年用于未经治疗的套细胞淋巴瘤。硼替佐米在轻链淀粉样变性、淋巴浆细胞淋巴瘤/华氏巨球蛋白血症和外周 T 细胞淋巴瘤中作为单一药物和与其他药物联合使用也显示出临床疗效。此外，还需要进行持续的临床研究来确认其对惰性和侵袭性 B 细胞非霍奇金淋巴瘤和急性白血病患者的价值。
