Novartis Pharmaceuticals, Florham Park, NJ, USA.
J Hematol Oncol. 2010 Nov 23;3:45. doi: 10.1186/1756-8722-3-45.
Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR) pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.
发现能够延长淋巴瘤患者生存时间且毒性低于现有药物的新疗法是目前迫切需要解决的问题。我们对淋巴瘤的分子发病机制有了更好的了解,如异常信号转导通路,这导致了靶向治疗药物的发现和发展。泛素-蛋白酶体和 Akt/哺乳动物雷帕霉素靶蛋白(mTOR)途径是药物开发中靶向的病理机制的例子。硼替佐米(一种小分子蛋白酶抑制剂)和 mTOR 抑制剂替西罗莫司、依维莫司和瑞达福林是目前正在研究用于治疗侵袭性、复发/难治性淋巴瘤的靶向治疗药物。这篇综述将讨论 mTOR 抑制剂和其他小分子靶向治疗药物治疗淋巴瘤的理论基础,并总结其初步和正在进行的研究结果。