Some neuroblastoma tumors are addicts, Delloye-Bourgeois et al. report on page 833. The tumor cells need a steady supply of a molecule called netrin-1, and they get their fix by making the compound themselves. Forcing the cells to go cold turkey could provide a new treatment for neuroblastoma, one of the most common childhood cancers.
Even healthy cells are often poised on the verge of death. Unless so-called dependence receptors receive continual stimulation, the cells kill themselves. One molecule that activates these receptors is netrin-1, a protein that is needed for normal neural development. Previous studies showed that certain breast and lung tumors pump out large amounts of netrin-1, suggesting that they rely on the molecule for survival.
Delloye-Bourgeois et al. now show that netrin-1 is also necessary for neuroblastoma. The most aggressive tumors manufactured extra netrin-1, the researchers found, and production of the molecule affected patients’ prognosis. Ninety percent of infants with tumors that made little netrin-1 were alive after five years, but only 48% of infants with tumors that produced copious netrin-1 survived that long.
These findings suggest that blocking netrin-1 curbs tumor growth. Indeed, eliminating netrin-1 in tumor cell lines led to their demise. And when the team implanted neuroblastoma tumors into chicken embryos and then neutralized netrin-1, the tumors shrank and were less likely to metastasize.
Cancers sometimes break their dependence on receptor stimulation by jettisoning the receptors. But neuroblastoma tumors didn't do that. Instead, some neuroblastomas feed their own addiction by manufacturing more netrin-1, thus preventing apoptosis. The researchers have recently begun preclinical studies on two netrin-1–blocking compounds that might provide an alternative to chemotherapy and radiation.
