TY - JOUR
T1 - From single-target to cellular niche targeting in Crohn's disease
T2 - intercepting bad communications
AU - Nayar, Shikha
AU - Cho, Judy H.
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Crohn's disease
KW - Genetics and genomics
KW - Myeloid cells
KW - Personalised therapeutics
KW - Stromal cells
KW - anti-TNF therapy
UR - http://www.scopus.com/inward/record.url?scp=85118690925&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2021.103690
DO - 10.1016/j.ebiom.2021.103690
M3 - Review article
C2 - 34773892
AN - SCOPUS:85118690925
SN - 2352-3964
VL - 74
JO - eBioMedicine
JF - eBioMedicine
M1 - 103690
ER -