Four New Targets Found for Breast Cancer

Protein Receptors, Enzyme Often Over-Produced

Three protein receptors and an enzyme that often are over-produced in several types of cancer also play roles in breast cancer.

A team of researchers, led by scientists at M. D. Anderson, reported its findings on lysophosphatidic acid (LPA) receptors (LPA1, LPA2, and LPA3) and the LPA-producing enzyme, autotaxin, in the June edition of Cancer Cell.

Significance of study

LPA binds to protein-coupled receptors to spark normal cell proliferation, viability, production of growth factors and survival.

"Lysophosphatidic acid is the single most potent cellular survival factor," says

Gordon Mills, M.D., Ph.D., professor and chair of M. D. Anderson's Department of Systems Biology and senior author on the paper.

But, this research shows that the powerful LPA network can be hijacked to initiate breast cancer and fuel tumor growth, invasion and metastasis, Mills says.

Research methods

Using a strain of mice that is highly resistant to breast cancer, the researchers created four new genetically modified strains. Each type of mouse made high levels of one of the receptors or autotaxin.

Primary results

At 24 months, none of the 44 original cancer-resistant mice developed breast cancer. One case of inflammation and two cases of hyperplasia (a potentially precancerous accumulation of cells) were noted.

In the mice that expressed the receptors or autotaxin, cancer incidence ranged from 32% to 52.8%. Invasive and metastatic tumors were present to varying degrees, with 45.5% of the tumors in the LPA3 strain metastasizing (spreading to other parts of the body).

What’s next?

While these agents have been suspected in breast cancer previously, this is the first definitive research that they can increase risk.

"We've compiled lots of evidence that they’re associated with cancer; what's been missing is proof that they could cause cancer," Mills says. "There are no questions left. They should be targeted."

A number of drugs that are in preclinical development target the receptors and autotaxin.

"Now we have transgenic mouse models to test drugs to go forward against these targets," Mills says.

Adapted by Dawn Dorsey from an M. D. Anderson news release.