Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations

Abstract The effect of scheduling of targeted therapy combinations on drug resistance is underexplored in triple-negative breast cancer (TNBC). TNBC constitutes heterogeneous cancer cell populations the composition of which can change dynamically during treatment resulting in the selection of resist...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Gauri A. Patwardhan, Michal Marczyk, Vikram B. Wali, David F. Stern, Lajos Pusztai, Christos Hatzis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/2761058a831d4c5bb0c7d0fdb6e51e5e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2761058a831d4c5bb0c7d0fdb6e51e5e
record_format	dspace
spelling	oai:doaj.org-article:2761058a831d4c5bb0c7d0fdb6e51e5e2021-12-02T15:00:58ZTreatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations10.1038/s41523-021-00270-42374-4677https://doaj.org/article/2761058a831d4c5bb0c7d0fdb6e51e5e2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00270-4https://doaj.org/toc/2374-4677Abstract The effect of scheduling of targeted therapy combinations on drug resistance is underexplored in triple-negative breast cancer (TNBC). TNBC constitutes heterogeneous cancer cell populations the composition of which can change dynamically during treatment resulting in the selection of resistant clones with a fitness advantage. We evaluated crizotinib (ALK/MET inhibitor) and navitoclax (ABT-263; Bcl-2/Bcl-xL inhibitor) combinations in a large design consisting of 696 two-cycle sequential and concomitant treatment regimens with varying treatment dose, duration, and drug holiday length over a 26-day period in MDA-MB-231 TNBC cells and found that patterns of resistance depend on the schedule and sequence in which the drugs are given. Further, we tracked the clonal dynamics and mechanisms of resistance using DNA-integrated barcodes and single-cell RNA sequencing. Our study suggests that longer formats of treatment schedules in vitro screening assays are required to understand the effects of resistance and guide more realistically in vivo and clinical studies.Gauri A. PatwardhanMichal MarczykVikram B. WaliDavid F. SternLajos PusztaiChristos HatzisNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Gauri A. Patwardhan Michal Marczyk Vikram B. Wali David F. Stern Lajos Pusztai Christos Hatzis Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
description	Abstract The effect of scheduling of targeted therapy combinations on drug resistance is underexplored in triple-negative breast cancer (TNBC). TNBC constitutes heterogeneous cancer cell populations the composition of which can change dynamically during treatment resulting in the selection of resistant clones with a fitness advantage. We evaluated crizotinib (ALK/MET inhibitor) and navitoclax (ABT-263; Bcl-2/Bcl-xL inhibitor) combinations in a large design consisting of 696 two-cycle sequential and concomitant treatment regimens with varying treatment dose, duration, and drug holiday length over a 26-day period in MDA-MB-231 TNBC cells and found that patterns of resistance depend on the schedule and sequence in which the drugs are given. Further, we tracked the clonal dynamics and mechanisms of resistance using DNA-integrated barcodes and single-cell RNA sequencing. Our study suggests that longer formats of treatment schedules in vitro screening assays are required to understand the effects of resistance and guide more realistically in vivo and clinical studies.
format	article
author	Gauri A. Patwardhan Michal Marczyk Vikram B. Wali David F. Stern Lajos Pusztai Christos Hatzis
author_facet	Gauri A. Patwardhan Michal Marczyk Vikram B. Wali David F. Stern Lajos Pusztai Christos Hatzis
author_sort	Gauri A. Patwardhan
title	Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
title_short	Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
title_full	Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
title_fullStr	Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
title_full_unstemmed	Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
title_sort	treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2761058a831d4c5bb0c7d0fdb6e51e5e
work_keys_str_mv	AT gauriapatwardhan treatmentschedulingeffectsontheevolutionofdrugresistanceinheterogeneouscancercellpopulations AT michalmarczyk treatmentschedulingeffectsontheevolutionofdrugresistanceinheterogeneouscancercellpopulations AT vikrambwali treatmentschedulingeffectsontheevolutionofdrugresistanceinheterogeneouscancercellpopulations AT davidfstern treatmentschedulingeffectsontheevolutionofdrugresistanceinheterogeneouscancercellpopulations AT lajospusztai treatmentschedulingeffectsontheevolutionofdrugresistanceinheterogeneouscancercellpopulations AT christoshatzis treatmentschedulingeffectsontheevolutionofdrugresistanceinheterogeneouscancercellpopulations
_version_	1718389127799373824

Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations

Ejemplares similares