Pharmacological analysis of CFTR variants of cystic fibrosis using stem cell-derived organoids.
Drug Discov Today
; 24(11): 2126-2138, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31173911
ABSTRACT
Cystic fibrosis (CF) is a life-shortening genetic disease caused by mutations of CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator. Despite considerable progress in CF therapies, targeting specific CFTR genotypes based on small molecules has been hindered because of the substantial genetic heterogeneity of CFTR mutations in patients with CF, which is difficult to assess by animal models in vivo. There are broadly four classes (e.g., II, III, and IV) of CF genotypes that differentially respond to current CF drugs (e.g., VX-770 and VX-809). In this review, we shed light on the pharmacogenomics of diverse CFTR mutations and the emerging role of stem cell-based organoids in predicting the CF drug response. We discuss mechanisms that underlie differential CF drug responses both in organoid-based assays and in CF clinical trials, thereby facilitating the precision design of safer and more effective therapies for individual patients with CF.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre
/
Organoides
/
Regulador de Conductancia de Transmembrana de Fibrosis Quística
/
Fibrosis Quística
/
Variantes Farmacogenómicas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Drug Discov Today
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2019
Tipo del documento:
Article