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

Biomolecules

卷:12

Kishore Hari¹  Mohit Kumar Jolly¹  Srisairam Achuthan²  Rishov Chatterjee²  Maneesh Jain³  Surinder Kumar Batra³  Mohd W. Nasser³  Govindan Rangarajan⁴  Anusha Nathan⁵  Linlin Guo⁵  Atish Mohanty⁵  Saumya Srivastava⁵  Ravi Salgia⁵  Arin Nam⁵  Sourabh Kotnala⁵  Erminia Massarelli⁵  Prakash Kulkarni⁵  Herbert Levine⁶  Supriyo Bhattacharya⁷ 

[1] Center for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India;

[2] Center for Informatics, Division of Research Informatics, City of Hope National Medical Center, Duarte, CA 91010, USA;

[3] Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA;

[4] Department of Mathematics, Indian Institute of Science, Bangalore 560012, India;

[5] Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA;

[6] Department of Physics, Northeastern University, Boston, MA 02115, USA;

[7] Integrative Genomics Core, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA;

关键词: chemoresistance;    cisplatin;    lung cancer;    evolutionary game theory;    group behavior;    persister trait;   

DOI  :  10.3390/biom12010008

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown