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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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