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Fitness bottlenecks as a therapeutic vulnerability in osteosarcoma

PIs: Jason Somarelli and Tom Schultz (Duke)

CHDI/TriCEM Pilot Research Grant

Osteosarcoma is the most common primary bone cancer in children. The major causes of death for nearly all kids with osteosarcoma are the metastatic spread of cells throughout the body that no longer respond to anti-cancer drugs. Most of these cancers evolve to become more metastatic and drug-resistant over time. During this evolutionary process, almost all of the osteosarcoma cells die as they encounter the harsh environments outside the tumor. These harsh environments can include low nutrients, high physical stresses, such as pressure and sheer forces, and exposure to drug treatments. These harsh environments when most osteosarcoma cells die and a few are left behind are known as population bottlenecks. We think these bottlenecks are the best times to kill the few remaining osteosarcoma cells and stop the disease altogether. In this project, we are developing a system to track bottlenecks and identify the genes that are turned on during each time a bottleneck occurs. We think the genes that are turned on during bottlenecks are the best candidates for new drugs to eradicate metastatic, drug-resistant osteosarcoma.

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