Fox Chase Cancer Center, Philadelphia, PA, USA.
Division of Oncology, Washington University Medical School, St. Louis, MO, USA.
Target Oncol. 2018 Jun;13(3):257-267. doi: 10.1007/s11523-018-0560-7.
Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma.
抗细胞凋亡是癌症的特征之一，B 细胞淋巴瘤 2（BCL-2）蛋白家族成员是细胞凋亡的核心调节剂。许多癌症通过上调 BCL-2 和其他家族成员对化疗和细胞凋亡产生耐药性，使这些蛋白成为癌症治疗的有吸引力的靶点。 Venetoclax 是一种口服小分子凋亡刺激剂，通过作为 BCL-2 同源结构域 3（BH3）模拟物靶向 BCL-2 蛋白。该药已在美国和欧盟获批作为单药治疗某些慢性淋巴细胞白血病（CLL）患者，目前正在进行多发性骨髓瘤（MM）的 III 期临床开发，以及急性髓系白血病和几种 B 细胞恶性肿瘤的 II 期或 I/II 临床试验，包括弥漫性大 B 细胞淋巴瘤、华氏巨球蛋白血症、滤泡性淋巴瘤和套细胞淋巴瘤。
