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

Arin Nam, Atish Mohanty, Supriyo Bhattacharya, Sourabh Kotnala, Srisairam Achuthan, Kishore Hari, Saumya Srivastava, Linlin Guo, Anusha Nathan, Rishov Chatterjee, Maneesh Jain, Mohd W. Nasser, Surinder Kumar Batra, Govindan Rangarajan, Erminia Massarelli, Herbert Levine, Mohit Kumar Jolly, Prakash Kulkarni, Ravi Salgia

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number8
JournalBiomolecules
Volume12
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Chemoresistance
  • Cisplatin
  • Evolutionary game theory
  • Group behavior
  • Lung cancer
  • Persister trait
  • Phenotypic switching

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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