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抗癌新药选择性刺激癌细胞凋亡

近日,研究人员开发出一种新抗癌药物,可克服目前癌症治疗方法的副作用,相关研究发表在1月7日的《NATURE MEDICINE》杂志上。

近日,研究人员开发出一种新抗癌药物,可克服目前癌症治疗方法的副作用,相关研究发表在1月7日的《NATURE MEDICINE》杂志上。

对BCL族促存活蛋白的抑制是一种具有前景的抗癌手段,但是族内蛋白的相似性却给特定试剂的研发带来难处。研究人员修改了已有的抗BCL药物,研制出一种能更好地特定识别BCL-2的药物且降低其对BCL-XL的亲和性,从而降低血小板毒性。

科学家表示,该药物在活体实验中对数种肿瘤类型都有效,其中有三位难治性白血病患者的治疗副作用降低,该药物的治疗前景以及安全性将在未来癌症促凋亡疗法的应用中发挥促进作用。

了解更多:

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

Nature Medicine (2013) doi:10.1038/nm.3048

Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2–like 1 (BCL-XL), which has shown clinical efficacy in some BCL-2–dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-XL inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2–selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2–dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2–dependent hematological cancers.

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