UCSD Researchers Discovered a Cancer-Promoting Molecule and Are Making Strides in Stopping it

Researchers at the University of California San Diego (UCSD) School of Medicine have discovered a leukemia-promoting molecule, and research data shows that they are making significant strides in stopping it.

UCSD researchers have found that CD98, a cell surface molecule that controls how cells attach to one another, helps the spread of Acute Myeloid Leikemia (AML), a stubborn form of cancer known for its resistance to drugs and other treatment.

The discovery of the surface molecule’s relationship with the cancer led them to attempt to fight the molecule with the anti-CD98 antibody and the therapeutic antibody IGN523. So far, their discovery looks promising.

The study, published Thursday by Cancer Cell, shows that the antibody blocks AML growth in patient derived cells and mouse models.

They determined CD98’s role in AML by engineering mouse models without the molecule and saw that the absence of CD98 blocked growth and increased survival. Further research revealed that leukemia cells lacking CD98 had fewer stable connections with blood vessel lining, which are necessary for AML growth.

After testing subjects that lacked CD98 completely, researchers moved to fighting the surface molecule with anti-CD98 and IGN523, a humanized antibody that binds to CD98 and renders it ineffective.

They found that IGN523 blocks AML growth in mouse models and in human cells, as well as human cells transplanted into mice, while anti-CD98 treatments completely eliminated AML cells.

According to Tannishtha Reya, PhD, professor of pharmacology at UC San Diego School of Medicine and co-senior author of the study, the data suggests that AML is unable to establish itself without CD98 and that blocking the molecule with anti-CD98 could be beneficial to children and adults.

"Many of the models we used in this work were based on mutations found in childhood AML,” Reya said. "While many childhood cancers have become very treatable, childhood AML continues to have a high rate of relapse and death. We plan to work with pediatric oncologists to test if anti-CD98 agents can be effective against pediatric AML, and whether it can improve responses to current treatments. I think this is particularly important to pursue since the anti-CD98 antibody has already been through phase I trials, and could be more easily positioned to test in drug-resistant pediatric AML."

An estimated 10,430 people in the United States alone will die from AML in 2016, according to the American Cancer Society.

Approximately 500 children in the U.S. are diagnosed with AML each year, and according to St. Jude Children’s Research Hospital, it is the most common second cancer among children being treated for other cancers.

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