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New findings identify key protein involved in fast-spreading cancers

BY AMY ADAMS

Researchers at the School of Medicine have found a protein that may explain why tumors in a low-oxygen environment are more deadly.

The findings, which were published April 27 in Nature, reveal that tumors that are hypoxic—low in oxygen—make a protein called lysyl oxidase that helps the tumor spread to other organs. Lysyl oxidase, or LOX, could be a good target for future cancer therapies, the researchers said.

"All tumors have the potential to spread," said lead author Amato Giaccia, MD, professor of radiation oncology. "A low-oxygen environment dials up that potential, and now we know why."

Hypoxia is caused when the supply of oxygen from the bloodstream fails to meet demand from body tissues, such as tumors. Hypoxic tumors can be found in many parts of the body. For this study, the researchers examined both breast tumors and head and neck tumors. In each case, patients whose tumors made high levels of LOX were more likely to have cancers that spread and to die of the disease.

The question is whether blocking LOX could also slow the cancer's spread. To find out, the researchers grew human cancers making high levels of LOX in mice. Using three different methods of shutting down LOX production, they found that the tumors were less likely to spread than tumors producing LOX unchecked.

Giaccia said blocking LOX in patients with hypoxic tumors has promise as a new therapy. He added that there are several ways of telling whether a tumor is hypoxic and therefore likely to be producing LOX. What's more, one of the methods used to block LOX in mice was an antibody, the same type of molecule as Herceptin, which has dramatically improved outcomes in people with some types of breast tumors.

A therapy that targets LOX-producing tumors would be particularly exciting given that these are among the deadliest cancers. Giaccia said human trials could start as soon as three years from now.

The group is now looking at the relationship between LOX-production and hypoxia in other types of tumors including lung and colon.

Other Stanford researchers who were involved in the work include postdoctoral fellows Janine Erler, PhD, and Kevin Bennewith, PhD; research mathematician Monica Nicolau, PhD; Christina Kong, MD, assistant professor of pathology; Quynh-Thu Le, MD, associate professor of radiation oncology, and Stefanie Jeffrey, MD, associate professor of surgery.