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Instead of killing tumor cells outright, doctors are exploring a new anti-cancer strategy that subtly hardens the cells so they can’t invade new areas of the body.

Scientists have identified a compound called 4-HAP that shows promise for stiffening pancreatic cancer cells. They now expect to use the new screening method that found the potential drug to look for agents that make other types of cancer too rigid to spread.

Octopus or lobster

“We think that being relatively soft lets invading cancer cells slip through the body and colonize new areas,” says lead researcher Alexandra Surcel.

“You can envision an octopus having a much easier time getting through a small opening than would a lobster. 4-HAP seems to make the cancer cells more like the lobster.”

Published online in the Proceedings of the National Academy of Sciences, the research has potential advantages over traditional chemotherapy, scientists say.

“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,” says Douglas Robinson, professor of cell biology at Johns Hopkins University School of Medicine.

“We think the new screening system we devised will help identify drugs for many other diseases as well.”

Cancer cell shape

The roots of the project go back to 1997, when Robinson, then a postdoctoral fellow, first had the idea that better understanding how a cell divides in 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 cell shape might be used to stall disease progress.

Surcel joined Robinson’s laboratory in 2008 as a postdoctoral fellow and began working on a screen for molecules that tweak cell shape. Most drug screens look for an effect on a specific biochemical “pathway” linked to a disease. By contrast, the new method is based on the end result for a whole cell.

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.

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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.

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 says.

But even if that doesn’t happen, the study demonstrates that the new drug screen has great potential, he says.

Other researchers from Johns Hopkins and from University of Chicago are coauthors of the study.

The National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Sol Goldman Pancreatic Cancer Center provided funding.

Source: Johns Hopkins University