The team collaborated to identify a compound, which they named metarrestin, that stopped tumor metastasis in multiple animal models. Mice treated with metarrestin also had fewer tumors and lived longer than mice that did not receive treatment.
Many drugs are aimed at stopping cancer growth and killing cancer cells. However, there is no single approved drug specifically aimed at treating metastasis.
In patients, metarrestin potentially could be effective as a therapy after cancer surgery. Because advanced cancers are difficult to completely remove with surgery, doctors typically give chemotherapy to try to kill undetected cancer cells left behind and prevent the cancer from coming back. Metarrestin could be added to such standard drug therapy.
Metarrestin breaks down an incompletely understood component of cancer cells called the perinucleolar compartment (PNC). PNCs are found only in cancer cells, and in a higher number of cells in advanced cancer, when it has spread to other sites in the body.
A team from Northwestern University Feinberg School of Medicine, Chicago, showed early on that the more cancer cells with PNCs in a tumor, the more likely it would spread. Her findings suggested that reducing PNCs might translate to less cancer progression and possibly better outcomes in patients.
To test these ideas, they used National Center for Advancing Translational Sciences (NCATS) expertise in screening, chemistry, compound development and testing to evaluate more than 140,000 compounds for their potential effectiveness in eliminating PNCs in cells in advanced cancer.
While nearly 100 compounds initially showed some activity, the investigators identified one compound that could effectively break down PNCs in advanced prostate cancer cells. With the help of researchers at the University of Kansas, Lawrence, they modified the compound to make it work better as a potential drug and evaluated the effects of the molecule in different assays, or tests, in the laboratory. They found that metarrestin could block the way prostate and pancreatic cancer cells spread.
The group evaluated the effects — including toxicity — of metarrestin in pancreatic cancer mouse models. The investigators found that it prevented the further spread of pancreatic cancer by disrupting the protein-making machinery of cancer cells, and mice treated with metarrestin lived longer than mice without treatment.