Targeting pan-essential genes in cancer: Challenges and opportunities.

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.
Competing Interests: Declaration of interests W.R.S. is a board or SAB member and holds equity in Ideaya Biosciences, Civetta Therapeutics, and Bluebird bio and has consulted for Array, Astex, Dynamo Therapeutics, Epidarex Capital, Ipsen, PearlRiver Therapeutics, Sanofi, Servier and Syndax Pharmaceuticals, and receives research funding from Pfizer Pharmaceuticals, Merck Pharmaceuticals, Ideaya Biosciences and Ridgeline Discovery. W.R.S. is a co-patent holder on EGFR mutation diagnostic patents. T.I. is an employee and shareholder of Scorpion Therapeutics.
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