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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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Detalles Bibliográficos
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
Descripción
Sumario: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.