Targeting cancer drug resistance utilizing organoid technology - 13/01/23
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Abstract |
Cancer organoids generated from 3D in vitro cell cultures have contributed to the study of drug resistance. Maintenance of genomic and transcriptomic similarity between organoids and parental cancer allows organoids to have the ability of accurate prediction in drug resistance testing. Protocols of establishing therapy-sensitive and therapy-resistant organoids are concluded in two aspects, which are generated directly from respective patients’ cancer and by induction of anti-cancer drug. Genomic and transcriptomic analyses and gene editing have been applied to organoid studies to identify key targets in drug resistance and FGFR3, KHDRBS3, lnc-RP11–536 K7.3 and FBN1 were found to be key targets. Furthermore, mechanisms contributing to resistance have been identified, including metabolic adaptation, activation of DNA damage response, defects in apoptosis, reduced cellular senescence, cellular plasticity, subpopulation interactions and gene fusions. Additionally, cancer stem cells (CSCs) have been verified to be involved in drug resistance utilizing organoid technology. Reversal of drug resistance can be achieved by targeting key genes and CSCs in cancer organoids. In this review, we summarize applications of organoids to cancer drug resistance research, indicating prospects and limitations.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Organoids have potential in drug resistance testing for the accurate prediction of drug response. |
• | Therapy-resistant organoids can be generated directly from respective patients’ cancer and by induction of anti-cancer drug. |
• | Many key targets have been discovered utilizing organoid technology through genomic and transcriptomic analysis. |
• | Organoids facilitate the exploration of resistance mechanisms related to CSCs. |
Keywords : Organoid, Cancer, Drug resistance, Resistance mechanism, Drug resistance testing, Reversal of drug resistance
Plan
Vol 158
Article 114098- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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