Dynamic phenotypic switching and group behavior help non-small cell lung cancer cells evade chemotherapy

Nam, A and Mohanty, A and Bhattacharya, S and Kotnala, S and Achuthan, S and Hari, K and Srivastava, S and Guo, L and Nathan, A and Chatterjee, R and Jain, M and Nasser, MW and Batra, SK and Rangarajan, G and Massarelli, E and Levine, H and Jolly, MK and Kulkarni, P and Salgia, R (2022) Dynamic phenotypic switching and group behavior help non-small cell lung cancer cells evade chemotherapy. In: Biomolecules, 12 (1).

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Abstract

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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type:	Journal Article
Publication:	Biomolecules
Publisher:	MDPI
Additional Information:	The copyright for this article belongs to Authors
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	20 Jan 2022 06:51
Last Modified:	20 Jan 2022 06:51
URI:	http://eprints.iisc.ac.in/id/eprint/70977

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