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 ∼40% of patients, likely due to incomplete cellular targeting and delayed treatment institution. While single-target therapeutics have been highly effective for some CD patients, substantia...

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Autores principales:	Shikha Nayar, Judy H. Cho
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Crohn's disease Personalised therapeutics Stromal cells Myeloid cells anti-TNF therapy Genetics and genomics Medicine R Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2edd0d56275e427b91380fd2fdfcbd3a
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spelling	oai:doaj.org-article:2edd0d56275e427b91380fd2fdfcbd3a2021-11-12T04:40:48ZFrom single-target to cellular niche targeting in Crohn's disease: intercepting bad communications2352-396410.1016/j.ebiom.2021.103690https://doaj.org/article/2edd0d56275e427b91380fd2fdfcbd3a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352396421004849https://doaj.org/toc/2352-3964The mainstay of moderate to severe Crohn's disease (CD), anti-TNF treatment, shows no clinical benefit in ∼40% of patients, likely due to incomplete cellular targeting and delayed treatment institution. While single-target 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.Shikha NayarJudy H. ChoElsevierarticleCrohn's diseasePersonalised therapeuticsStromal cellsMyeloid cellsanti-TNF therapyGenetics and genomicsMedicineRMedicine (General)R5-920ENEBioMedicine, Vol 74, Iss , Pp 103690- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Crohn's disease Personalised therapeutics Stromal cells Myeloid cells anti-TNF therapy Genetics and genomics Medicine R Medicine (General) R5-920
spellingShingle	Crohn's disease Personalised therapeutics Stromal cells Myeloid cells anti-TNF therapy Genetics and genomics Medicine R Medicine (General) R5-920 Shikha Nayar Judy H. Cho From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications
description	The mainstay of moderate to severe Crohn's disease (CD), anti-TNF treatment, shows no clinical benefit in ∼40% of patients, likely due to incomplete cellular targeting and delayed treatment institution. While single-target 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.
format	article
author	Shikha Nayar Judy H. Cho
author_facet	Shikha Nayar Judy H. Cho
author_sort	Shikha Nayar
title	From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications
title_short	From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications
title_full	From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications
title_fullStr	From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications
title_full_unstemmed	From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications
title_sort	from single-target to cellular niche targeting in crohn's disease: intercepting bad communications
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/2edd0d56275e427b91380fd2fdfcbd3a
work_keys_str_mv	AT shikhanayar fromsingletargettocellularnichetargetingincrohnsdiseaseinterceptingbadcommunications AT judyhcho fromsingletargettocellularnichetargetingincrohnsdiseaseinterceptingbadcommunications
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From single-target to cellular niche targeting in Crohn's disease: intercepting bad communications

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