Clues to how aggressive sarcomas beat chemotherapy drugs

Memphis, Tennessee, December 18, 2015

Researchers Alessandra d'Azzo, Ph.D., and Eda Machado, Ph.D.

St. Jude researchers (from left), Alessandra d'Azzo, Ph.D., of the St. Jude Department of Genetics and postdoctoral fellow Eda Machado, Ph.D., are the corresponding and first authors of research that details how aggressive sarcomas hijack an export pathway in cells to promote cancer progression and resist chemotherapy. Researchers also showed the process may be reversible using medications like the hypertension drug verapamil.

Among the questions that puzzle researchers are how malignant tumors invade nearby tissues and resist chemotherapy.

Scientists at St. Jude Children’s Research Hospital have discovered a strategy that a cancer of the muscle and soft tissue called sarcoma uses to accomplish the tasks. Researchers also showed the process may be thwarted using medications, including the common blood pressure drug verapamil.

In the lab, scientists found that some sarcomas can hijack a process that cells use to remove different molecules. As the sarcomas become more aggressive, they set the stage to spread into healthy tissue by increasing the clearance of molecules via this process.

Tumor cells use the same process to isolate and remove certain chemotherapy drugs before those drugs have a chance to work. But researchers found that treating the tumor cells with verapamil reduces such exports and restores sensitivity to chemotherapy.

“This study helps to answer a central question of cancer biology and identifies a process that might prove useful to combat drug resistance and tumor spread,” said Alessandra d’Azzo, PhD, of the St. Jude Department of Genetics.

The research was published in the journal Science Advances.

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