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Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy

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Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA
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Integrative Genomics Core, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
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Center for Informatics, Division of Research Informatics, City of Hope National Medical Center, Duarte, CA 91010, USA
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Center for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India
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Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
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Department of Mathematics, Indian Institute of Science, Bangalore 560012, India
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Center for Neuroscience, Indian Institute of Science, Bangalore 560012, India
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Department of Physics, Northeastern University, Boston, MA 02115, USA
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Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
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Department of Medical Oncology and Therapeutics Research, Arthur & Rosalie Kaplan Endowed Chair in Medical Oncology, 1500 E. Duarte Road, Duarte, CA 91010, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Present address: Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA.
Academic Editor: Vladimir N. Uversky
Biomolecules 2022, 12(1), 8; https://doi.org/10.3390/biom12010008
Received: 22 November 2021 / Revised: 14 December 2021 / Accepted: 17 December 2021 / Published: 21 December 2021
(This article belongs to the Section Bioinformatics and Systems Biology)
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. View Full-Text
Keywords: chemoresistance; cisplatin; lung cancer; evolutionary game theory; group behavior; persister trait; phenotypic switching chemoresistance; cisplatin; lung cancer; evolutionary game theory; group behavior; persister trait; phenotypic switching
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MDPI and ACS Style

Nam, A.; Mohanty, A.; Bhattacharya, S.; Kotnala, S.; Achuthan, S.; Hari, K.; Srivastava, S.; Guo, L.; Nathan, A.; Chatterjee, R.; Jain, M.; Nasser, M.W.; Batra, S.K.; Rangarajan, G.; Massarelli, E.; Levine, H.; Jolly, M.K.; Kulkarni, P.; Salgia, R. Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy. Biomolecules 2022, 12, 8. https://doi.org/10.3390/biom12010008

AMA Style

Nam A, Mohanty A, Bhattacharya S, Kotnala S, Achuthan S, Hari K, Srivastava S, Guo L, Nathan A, Chatterjee R, Jain M, Nasser MW, Batra SK, Rangarajan G, Massarelli E, Levine H, Jolly MK, Kulkarni P, Salgia R. Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy. Biomolecules. 2022; 12(1):8. https://doi.org/10.3390/biom12010008

Chicago/Turabian Style

Nam, Arin, Atish Mohanty, Supriyo Bhattacharya, Sourabh Kotnala, Srisairam Achuthan, Kishore Hari, Saumya Srivastava, Linlin Guo, Anusha Nathan, Rishov Chatterjee, Maneesh Jain, Mohd W. Nasser, Surinder K. Batra, Govindan Rangarajan, Erminia Massarelli, Herbert Levine, Mohit K. Jolly, Prakash Kulkarni, and Ravi Salgia. 2022. "Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy" Biomolecules 12, no. 1: 8. https://doi.org/10.3390/biom12010008

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