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Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy
Drug resistance, a major challenge in cancer therapy, is typically attributed to mutations and genetic heterogeneity. Emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance. However, the underlying mechanisms remain poorly understood. Here...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773639/ https://www.ncbi.nlm.nih.gov/pubmed/35053156 http://dx.doi.org/10.3390/biom12010008 |
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author | Nam, Arin Mohanty, Atish Bhattacharya, Supriyo Kotnala, Sourabh Achuthan, Srisairam Hari, Kishore Srivastava, Saumya Guo, Linlin Nathan, Anusha Chatterjee, Rishov Jain, Maneesh Nasser, Mohd W. Batra, Surinder Kumar Rangarajan, Govindan Massarelli, Erminia Levine, Herbert Jolly, Mohit Kumar Kulkarni, Prakash Salgia, Ravi |
author_facet | Nam, Arin Mohanty, Atish Bhattacharya, Supriyo Kotnala, Sourabh Achuthan, Srisairam Hari, Kishore Srivastava, Saumya Guo, Linlin Nathan, Anusha Chatterjee, Rishov Jain, Maneesh Nasser, Mohd W. Batra, Surinder Kumar Rangarajan, Govindan Massarelli, Erminia Levine, Herbert Jolly, Mohit Kumar Kulkarni, Prakash Salgia, Ravi |
author_sort | Nam, Arin |
collection | PubMed |
description | Drug resistance, a major challenge in cancer therapy, is typically attributed to mutations and genetic heterogeneity. Emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance. However, the underlying mechanisms remain poorly understood. Here, we present a new mathematical approach with game theoretical underpinnings that we developed to model real-time growth data of non-small cell lung cancer (NSCLC) cells and discern patterns in response to treatment with cisplatin. We show that the cisplatin-sensitive and cisplatin-tolerant NSCLC cells, when co-cultured in the absence or presence of the drug, display dynamic group behavior strategies. Tolerant cells exhibit a ‘persister-like’ behavior and are attenuated by sensitive cells; they also appear to ‘educate’ sensitive cells to evade chemotherapy. Further, tolerant cells can switch phenotypes to become sensitive, especially at low cisplatin concentrations. Finally, switching treatment from continuous to an intermittent regimen can attenuate the emergence of tolerant cells, suggesting that intermittent chemotherapy may improve outcomes in lung cancer. |
format | Online Article Text |
id | pubmed-8773639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87736392022-01-21 Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy Nam, Arin Mohanty, Atish Bhattacharya, Supriyo Kotnala, Sourabh Achuthan, Srisairam Hari, Kishore Srivastava, Saumya Guo, Linlin Nathan, Anusha Chatterjee, Rishov Jain, Maneesh Nasser, Mohd W. Batra, Surinder Kumar Rangarajan, Govindan Massarelli, Erminia Levine, Herbert Jolly, Mohit Kumar Kulkarni, Prakash Salgia, Ravi Biomolecules Article Drug resistance, a major challenge in cancer therapy, is typically attributed to mutations and genetic heterogeneity. Emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance. However, the underlying mechanisms remain poorly understood. Here, we present a new mathematical approach with game theoretical underpinnings that we developed to model real-time growth data of non-small cell lung cancer (NSCLC) cells and discern patterns in response to treatment with cisplatin. We show that the cisplatin-sensitive and cisplatin-tolerant NSCLC cells, when co-cultured in the absence or presence of the drug, display dynamic group behavior strategies. Tolerant cells exhibit a ‘persister-like’ behavior and are attenuated by sensitive cells; they also appear to ‘educate’ sensitive cells to evade chemotherapy. Further, tolerant cells can switch phenotypes to become sensitive, especially at low cisplatin concentrations. Finally, switching treatment from continuous to an intermittent regimen can attenuate the emergence of tolerant cells, suggesting that intermittent chemotherapy may improve outcomes in lung cancer. MDPI 2021-12-21 /pmc/articles/PMC8773639/ /pubmed/35053156 http://dx.doi.org/10.3390/biom12010008 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nam, Arin Mohanty, Atish Bhattacharya, Supriyo Kotnala, Sourabh Achuthan, Srisairam Hari, Kishore Srivastava, Saumya Guo, Linlin Nathan, Anusha Chatterjee, Rishov Jain, Maneesh Nasser, Mohd W. Batra, Surinder Kumar Rangarajan, Govindan Massarelli, Erminia Levine, Herbert Jolly, Mohit Kumar Kulkarni, Prakash Salgia, Ravi Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy |
title | Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy |
title_full | Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy |
title_fullStr | Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy |
title_full_unstemmed | Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy |
title_short | Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy |
title_sort | dynamic phenotypic switching and group behavior help non-small cell lung cancer cells evade chemotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773639/ https://www.ncbi.nlm.nih.gov/pubmed/35053156 http://dx.doi.org/10.3390/biom12010008 |
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