While many transcription factors can cause cancer, they often have essential functions in other tissues. Thus, total inhibition of a transcription factor kills cancer cells, but damages normal cells, often resulting in unacceptable toxicities in patients. This conundrum is exemplified in the field studying cancers driven by the Notch transcription factor in which clinical trials involving more than 600 patients treated with Notch inhibitors developed intolerable on-target toxicities. Thus, the challenge for the field is to find ways to selectively target the oncogenic functions of transcription factors, but spare the essential normal functions.
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