靶向癌症中的泛必需基因：挑战与机遇。
Targeting pan-essential genes in cancer: Challenges and opportunities.
机构信息
Broad Institute of Harvard and MIT, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Harvard and MIT, Cambridge, MA, USA.
出版信息
Cancer Cell. 2021 Apr 12;39(4):466-479. doi: 10.1016/j.ccell.2020.12.008. Epub 2021 Jan 14.
Abstract
Despite remarkable successes in the clinic, cancer targeted therapy development remains challenging and the failure rate is disappointingly high. This problem is partly due to the misapplication of the targeted therapy paradigm to therapeutics targeting pan-essential genes, which can result in therapeutics whereby efficacy is attenuated by dose-limiting toxicity. Here we summarize the key features of successful chemotherapy and targeted therapy agents, and use case studies to outline recurrent challenges to drug development efforts targeting pan-essential genes. Finally, we suggest strategies to avoid previous pitfalls for ongoing and future development of pan-essential therapeutics.
摘要
尽管在临床上取得了显著的成功，但癌症靶向治疗的发展仍然具有挑战性，失败率令人失望地高。这个问题部分是由于靶向治疗模式在针对泛必需基因的治疗中的错误应用，这可能导致治疗效果因剂量限制毒性而减弱。在这里，我们总结了成功的化疗和靶向治疗药物的关键特征，并通过案例研究概述了针对泛必需基因的药物开发工作中反复出现的挑战。最后，我们为正在进行和未来的泛必需治疗药物的开发提出了避免以前陷阱的策略。
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