Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy.
Biomolecules
; 12(1)2021 12 21.
Article
in En
| MEDLINE
| ID: mdl-35053156
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cisplatin
/
Carcinoma, Non-Small-Cell Lung
/
Drug Resistance, Neoplasm
/
Lung Neoplasms
/
Models, Biological
Limits:
Humans
Language:
En
Journal:
Biomolecules
Year:
2021
Document type:
Article
Affiliation country:
United States