Researchers at the Stanford University School of Medicine have found a protein that may explain why tumors in a low-oxygen environment are more deadly.
The findings, to be published April 27 in the journal 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 say.
"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 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 protein as HER2/Neu, which has dramatically improved outcomes in people with some types of breast tumors.
A therapy that specifically treats tumors producing LOX would be particularly exciting given that these are often among the deadliest cancers. Giaccia said trials in people 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 closely involved in the work include postdoctoral fellows Janine Erler, PhD, and Kevin Bennewith, PhD; Monica Nicolau, PhD, research mathematician; Christina Kong, MD, assistant professor of pathology; Quynh-Thu Le, MD, associate professor of radiation oncology, and Stefanie Jeffrey, MD, associate professor of surgery.
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