From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications

The mainstay of moderate to severe Crohn's disease (CD), anti-TNF treatment, shows no clinical benefit in similar to 40% of patients, likely due to incomplete cellular targeting and delayed treatment institution. While singletarget therapeutics have been highly effective for some CD patients, substantial limitations with respect to safety, efficacy, and long-term, complete remission remain. Deconvolution of the cellular and molecular circuitry of tissue lesions underscores the importance of combinatorial strategies targeting cellular niches. This review aims to evaluate current therapeutic approaches used to manage CD, and highlight recent advances to our cellular, genetic, and molecular understanding of mechanisms driving pathogenic niche activation in CD. We propose new frameworks outlining that combinatorial therapies, along with serial tissue sampling and studies guided by genetics and genomics, can advance on current treatment approaches and will inform newer strategies upon which we can move towards precision therapeutics in IBD. (C) 2021 The Author(s). Published by Elsevier B.V.

Automated summary

This review highlights the importance of combinatorial therapies and strategies guided by genetics and genomics in advancing current treatment approaches for Crohn's disease. The study aims to improve our understanding of the mechanisms driving pathogenic niche activation in CD and move towards precision therapeutics in IBD.