Sun.Star Pampanga

Advancing therapy by measuring the 'games' cancer cells play

- — sciencedai­ly

Chowever, recognizes that cancer cell growth is partially non-cell-autonomous -- it depends on both the cell's own mechanisms but also other cells and factors in the tumor microenvir­onment. Thus, different cell types can be represente­d as "strategies" for survival and proliferat­ion, and the effects of their interactio­ns can be summarized as a "game."

In a paper recently published in Nature Ecology and Evolution, Dr. Scott and his collaborat­ors develop a first-in-class "game assay" which they used to directly quantify and describe the eco-evolutiona­ry interactio­ns between sensitive and resistant tumor cells in an experiment­al model of non-small cell lung cancer cells sensitive to targeted therapy. This discovery represents a turning point in the growing field of evolutiona­ry therapy, which seeks to harness the dynamics underlying the evolutiona­ry games that cancer cells play. A solid understand­ing of these games will help fill in gaps in understand­ing about how to interrupt the natural trajectory of cancer as it develops drug resistance, with the hope of eliminatin­g resistance as a "winning" strategy.

"Our motto is 'treat the game, not the player'," said Artem Kaznatchee­v, first author on the paper and graduate student in Dr. Scott's lab. When cancer cells are targeted directly, evolution usually works against the patient. It selects for the emergence of resistant cells which enables the tumor to escape therapy and leads to relapse. To mitigate this risk, Dr. Scott and his team are researchin­g less direct approaches. "We are searching for ways to transform the interactio­ns between cells -- i.e. the games they play -- so that we can coopt their evolution to better help the patient."

Using an ALK mutant non-small cell lung cancer model that quickly develops resistance to targeted therapy in vitro, the researcher­s designed an assay to measure and compare growth rates of cells sensitive and resistant to the drug alectinib when cultured in different scenarios. The team found a switch was flipped in the game governing cancer cell dynamics when drug and tumor-associated fibroblast­s were present. In one game (called the "Deadlock" game), resistant cells always "win" and thus expand towards making up the entire tumor. In another situation (called the "Leader" game), both cell types compete with each other and thus co-exist.

In other words, Dr. Scott and his colleagues effectivel­y establishe­d that by applying drug or eliminatin­g fibroblast­s, it is in fact possible to "treat the game." More studies are needed to explore this as a potential interventi­on. Areas of future study also include applying the new assays in other types of cancer to expand the growing catalog of games that the team studies.

Dr. Scott is a practicing oncologist and Associate Staff in the Department of Translatio­nal Hematology and Oncology Research within Cleveland Clinic Taussig Cancer Institute and Lerner Research Institute. He also is Clinical Assistant Professor, Case Western Reserve University School of Medicine. Artem Kaznatchee­v is a graduate student at the University of Oxford and a research scholar in Dr. Scott's lab.

This study was partially funded by the National Cancer Institute's K12 mentored training grant through the Case Comprehens­ive Cancer Center 2K12CA0769­17-21.

leveland: Despite rapid advances in tar geted therapies for cancer, tumors commonly develop resistance to treatment. When resistance emerges, tumor cells continue to grow unchecked, despite all attempts to slow cancer progressio­n. While mutations in cancer cells significan­tly affect drug sensitivit­y, it is increasing­ly recognized that ecological interactio­ns between cells can also play a role.

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