Transforming targeted cancer therapy with PROTACs: A forward-looking perspective.

Small-molecule targeted protein degraders have in recent years made a great impact on the strategies of many industry and academic cancer research endeavours. We seek here to provide a concise perspective on the opportunities and challenges that lie ahead for bifunctional degrader molecules, so-called 'Proteolysis Targeting Chimeras (PROTACs),' in the context of cancer therapy. We highlight high-profile studies that support the potential for PROTAC approaches to broaden drug target scope, address drug resistance, enhance target selectivity and provide tissue specificity, but also assess where the modality is yet to fully deliver in these contexts. Future opportunities presented by the unique bifunctional nature of these molecules are also discussed.

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Déclaration de conflit d'intérêts

Conflict of interest statement William Farnaby: Declarations of interest: none. Manfred Koegl and Darryl McConnell are employees of Boehringer Ingelheim. Alessio Ciulli: A.C. is a scientific founder, shareholder, nonexecutive director, and consultant of Amphista Therapeutics, a company that is developing targeted protein degradation therapeutic platforms. The Ciulli laboratory receives or has received sponsored research support from Almirall, Amphista Therapeutics, Boehringer Ingelheim, Eisai, Nurix Therapeutics, and Ono Pharmaceutical.