Why Tumors Low in Oxygen Spread So Fast

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Stanford scientists identify protein involved in fast-spreading

cancers

STANFORD, Calif. - 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.

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