Investigation of evolutionary dynamics for drug resistance in 3D spheroid model system using cellular barcoding technology

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(9), P. e0291942 - e0291942

Published: Sept. 26, 2023

Complex evolutionary dynamics governing the drug resistance is one of major challenges in cancer treatment. Understanding these mechanisms requires a sequencing technology with higher resolution to delineate whether pre-existing or de novo are behind resistance. Combining this clinically very relevant model system, namely 3D spheroids, better mimicking tumorigenesis and have so far been lacking. Thus, we sought establish dabrafenib irinotecan resistant derivatives barcoded spheroids ultimate aim quantify selection-induced clonal identify genomic determinants system. We found that induced 3D-HT-29 3D-HCT-116 mediated by barcodes, indicating presence polyclonal Moreover, whole-exome analysis chromosomal gains mutations associated spheroids. Last, show also multiple detection upregulation efflux pumps, ABCB1 ABCG2, our spheroid Overall, present quantification for first time using cellular barcoding underlying

Language: Английский

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Patient-Derived Organoids: Past, Present, and Future

Interdisciplinary cancer research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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