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.

尽管在临床上取得了显着的成功，但癌症靶向治疗的开发仍然充满挑战，失败率也高得令人失望。这个问题的部分原因是靶向治疗范式错误地应用于针对泛必需基因的治疗，这可能导致治疗效果因剂量限制性毒性而减弱。在这里，我们总结了成功化疗和靶向治疗药物的关键特征，并利用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，我们提出了一些策略，以避免以前的陷阱，以促进泛必需疗法的持续和未来发展。