New cancer-fighting strategy is to harden cells to prevent metastasis

Existing cancer therapies are geared toward massacring tumor cells, but researchers have proposed a different strategy: subtly hardening cancer cells to prevent them from invading new areas of the body.

The research team devised a way of screening compounds for the desired effect, and they have identified a compound that shows promise in fighting pancreatic cancer. Their study appeared in the Proceedings of the National Academy of Sciences (2015; doi:10.1073/pnas.1412592112).

“This is a novel approach to cancer therapy that we believe could fight the disease with less potential for side effects and drug resistance than many current drugs,” said Douglas Robinson, PhD, a professor of cell biology in the Institute for Basic Biomedical Sciences at Johns Hopkins University School of Medicine in Baltimore, Maryland. “We think the new screening system we devised will help identify drugs for many other diseases, as well.”

The roots of the project go back to 1997, when Robinson, then a postdoctoral fellow, said he first had the idea that better understanding how a cell divides into two would shed light on how cells change shape in general. Since changes in cell shape figure into conditions from cancer to chronic obstructive pulmonary disease to degenerative nerve diseases, compounds that affect cells shape could turn out to stall disease progress.

A screen of thousands of molecules turned up 25 with the effect the team was looking for. Further studies revealed that one of them, 4-HAP, affected myosin II, a building block of the cell skeleton. In collaboration with another Johns Hopkins lab, led by Robert Anders, MD, PhD, an associate professor of pathology, Robinson's group identified changes in the amount of myosin II in pancreatic cancer cells as they spread from the original tumor into other areas of the body, a crucial step in progression of the disease.

The research team tested 4-HAP on lab-grown pancreatic cancer cells and found that it affected the myosin in their skeletons in a way that made them harder. “We think that being relatively soft lets invading cancer cells slip through the body and colonize new areas,” Surcel said.

The team is now testing 4-HAP in mice. The drug is already in use in some countries as a treatment for jaundice, so if it shows success against pancreatic cancer, it could potentially make it to market relatively quickly, Robinson said. But even if that does not happen, the study demonstrates that the new drug screen has great potential, he said.

The study was funded by the National Institute of General Medical Sciences (grant number GM66817), the National Institute of Allergy and Infectious Diseases (grant number AI099704), the National Cancer Institute (grant number T32 CA009243), and the Sol Goldman Pancreatic Cancer Center.

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