Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation

Adaptive therapy exploits the self-organization of tumor cells to delay the outgrowth of resistant subpopulations successfully. When the tumor has aggressive resistant subpopulations, the outcome of adaptive therapy was not superior to maximum tolerated dose therapy (MTD). To explore methods to impr...

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Autores principales:	Jiali Wang, Yixuan Zhang, Xiaoquan Liu, Haochen Liu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adaptive therapy reachability-based adaptive therapy restore index intra-competition osimertinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f29f0ba5366a444ebd69aa4b72ee743e
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spelling	oai:doaj.org-article:f29f0ba5366a444ebd69aa4b72ee743e2021-11-11T15:26:39ZOptimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation10.3390/cancers132152622072-6694https://doaj.org/article/f29f0ba5366a444ebd69aa4b72ee743e2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5262https://doaj.org/toc/2072-6694Adaptive therapy exploits the self-organization of tumor cells to delay the outgrowth of resistant subpopulations successfully. When the tumor has aggressive resistant subpopulations, the outcome of adaptive therapy was not superior to maximum tolerated dose therapy (MTD). To explore methods to improve the adaptive therapy’s performance of this case, the tumor system was constructed by osimertinib-sensitive and resistant cell lines and illustrated by the Lotka-Volterra model in this study. Restore index proposed to assess the system reachability can predict the duration of each treatment cycle. Then the threshold of the restore index was estimated to evaluate the timing of interrupting the treatment cycle and switching to high-frequency administration. The introduced reachability-based adaptive therapy and classic adaptive therapy were compared through simulation and animal experiments. The results suggested that reachability-based adaptive therapy showed advantages when the tumor has an aggressive resistant subpopulation. This study provides a feasible method for evaluating whether to continue the adaptive therapy treatment cycle or switch to high-frequency administration. This method improves the gain of adaptive therapy by taking into account the benefits of tumor intra-competition and the tumor control of killing sensitive subpopulation.Jiali WangYixuan ZhangXiaoquan LiuHaochen LiuMDPI AGarticleadaptive therapyreachability-based adaptive therapyrestore indexintra-competitionosimertinibNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5262, p 5262 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adaptive therapy reachability-based adaptive therapy restore index intra-competition osimertinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	adaptive therapy reachability-based adaptive therapy restore index intra-competition osimertinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jiali Wang Yixuan Zhang Xiaoquan Liu Haochen Liu Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation
description	Adaptive therapy exploits the self-organization of tumor cells to delay the outgrowth of resistant subpopulations successfully. When the tumor has aggressive resistant subpopulations, the outcome of adaptive therapy was not superior to maximum tolerated dose therapy (MTD). To explore methods to improve the adaptive therapy’s performance of this case, the tumor system was constructed by osimertinib-sensitive and resistant cell lines and illustrated by the Lotka-Volterra model in this study. Restore index proposed to assess the system reachability can predict the duration of each treatment cycle. Then the threshold of the restore index was estimated to evaluate the timing of interrupting the treatment cycle and switching to high-frequency administration. The introduced reachability-based adaptive therapy and classic adaptive therapy were compared through simulation and animal experiments. The results suggested that reachability-based adaptive therapy showed advantages when the tumor has an aggressive resistant subpopulation. This study provides a feasible method for evaluating whether to continue the adaptive therapy treatment cycle or switch to high-frequency administration. This method improves the gain of adaptive therapy by taking into account the benefits of tumor intra-competition and the tumor control of killing sensitive subpopulation.
format	article
author	Jiali Wang Yixuan Zhang Xiaoquan Liu Haochen Liu
author_facet	Jiali Wang Yixuan Zhang Xiaoquan Liu Haochen Liu
author_sort	Jiali Wang
title	Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation
title_short	Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation
title_full	Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation
title_fullStr	Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation
title_full_unstemmed	Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation
title_sort	optimizing adaptive therapy based on the reachability to tumor resistant subpopulation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f29f0ba5366a444ebd69aa4b72ee743e
work_keys_str_mv	AT jialiwang optimizingadaptivetherapybasedonthereachabilitytotumorresistantsubpopulation AT yixuanzhang optimizingadaptivetherapybasedonthereachabilitytotumorresistantsubpopulation AT xiaoquanliu optimizingadaptivetherapybasedonthereachabilitytotumorresistantsubpopulation AT haochenliu optimizingadaptivetherapybasedonthereachabilitytotumorresistantsubpopulation
_version_	1718435344483876864

Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation

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