For many patients with cancer, treatment resistance develops, leaving cancerous cells to continue to proliferate. Viewing the capability of cancer cells to develop resistance to drugs as a type of evolutionary game, researchers at the Cleveland Clinic developed a game assay using a model of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cells to measure and explain the interactions between drug-sensitive and drug-resistant cancer cells.
"Rather than searching for a 'silver bullet' to wipe out all resistant cells, which is unlikely, we are focused on preventing the resistant cells from taking over—from 'winning' every time," commented one of the study authors, Jacob Scott, MD, DPhil, of the Departments of Translational Hematology and Oncology Research and Radiation Oncology at the Cleveland Clinic. "If we can achieve this goal, we can effectively make cancer a chronic condition."
In the study, published in Nature Ecology and Evolution, the investigators used the game assay on a model of ALK-positive NSCLC that is resistant to the targeted therapy drug alectinib to measure and compare growth rates of drug-sensitive and drug-resistant cancer cells in different conditions. The game conditions differed based on the presence of cancer-associated fibroblasts and targeted therapy drugs. In one game condition, called the "Deadlock" game, drug-resistant cells beat drug-sensitive cells and took over the entire tumor. In another game condition, "Leader," both drug-resistant and drug-sensitive cancer cells made up the tumor, thereby coexisting. The researchers conclude from playing the game that only targeting the cancer cells with targeted therapy is not always effective. When targeted therapy is used, evolution works against the patient, allowing for the emergence of resistant cells leading the tumor to escape therapy and cause relapse.
Artem Kaznatcheev, first author on the paper and a graduate student in Dr. Scott's lab, emphasized the lesson learned from the study: "Our motto is 'treat the game, not the player.'"
For More Information
Kaznatcheev A, Peacock J, Basanta D, et al (2019). Fibroblasts and alectinib switch the evolutionary games played by non-small cell lung cancer. Nat Ecol Evol. [Epub ahead of print] DOI:10.1038/s41559-018-0768-z
Image courtesy of David Lapetina