Indiana University School of Medicine, Division of Hematology and Oncology, Department of Medicine, Indianapolis, IN 46202, USA.
Expert Opin Investig Drugs. 2011 Jul;20(7):1015-28. doi: 10.1517/13543784.2011.584869. Epub 2011 May 26.
Multiple myeloma (MM) remains incurable, indicating the need for continued investigation of innovative strategies. Recent progress in molecular biology has advanced the discovery of novel drugs for MM. ENMD-2076 is an orally bioavailable, multi-target kinase inhibitor with multiple mechanisms of action, including anti-proliferative and pro-apoptotic activity, and anti-angiogenic effects.
In this review, the authors summarize the preclinical in vitro and in vivo data that have formed the rationale for clinical investigation of ENMD-2076 in MM. In addition, the authors review the early clinical results of ENMD-2076 in MM and other malignancies, and speculate on potential avenues of future clinical research in the development of this drug for MM.
There is a strong preclinical rationale for investigating ENMD-2076 in MM that is confirmed by early clinical results in an ongoing Phase I trial in patients with relapsed or refractory MM. Optimal strategies for developing ENMD-2076 in MM will require better elucidation of its mechanism of action, investigation of biomarkers for response and development of rationale synergistic combinations with other active agents.
多发性骨髓瘤(MM)仍然无法治愈,这表明需要继续研究创新策略。分子生物学的最新进展推进了 MM 新型药物的发现。ENMD-2076 是一种口服生物可利用的多靶点激酶抑制剂,具有多种作用机制,包括抗增殖和促凋亡活性以及抗血管生成作用。
在这篇综述中,作者总结了形成 ENMD-2076 用于 MM 临床研究基础的临床前体外和体内数据。此外,作者还回顾了 ENMD-2076 在 MM 和其他恶性肿瘤中的早期临床结果,并推测了在 MM 中开发该药的未来临床研究的潜在途径。
ENMD-2076 在 MM 中的研究具有很强的临床前基础,这一点得到了正在进行的复发或难治性 MM 患者 I 期临床试验的早期临床结果的证实。开发 ENMD-2076 在 MM 中的最佳策略将需要更好地阐明其作用机制,研究反应的生物标志物,并与其他活性药物开发合理的协同组合。