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Combination of 2′-Fluoroadenine and 5′-Methylthioadenosine Shows Therapeutic Potential in Variety of Cancers

August 14, 2018

PHILADELPHIA (August 14, 2018) — Warren Kruger, PhD, a professor of cancer biology at Fox Chase Cancer Center, recently published a study in the journal Cancer Research describing a promising new combination therapy approach to killing tumor cells while sparing healthy cells. His approach builds on the understanding that many cancers, including pancreatic, non-small cell lung cancer, and certain brain and spinal cord cancers, cause the deletion of the MTAP gene.  

“Deletion of the MTAP gene is a common event in many types of human cancer,” Kruger said. “We found a way to specifically target MTAP-deleted cancer cells by using a two drug combination.”   

In this study, Kruger treated mice with a novel combination of a highly toxic drug (2′-fluoroadenine, known as 2FA) and a protective agent (5′-deoxy-5′-methylthioadenosine, known as MTA) that only protects cells with a functional MTAP gene.

“In effect, we are giving a powerful toxin to all cells in the body, but the same time are giving an antidote that only works in normal cells, but not tumor cells. Thus the tumor cells die, while the normal cells are spared,” he said.

The results of this preclinical work show that the combination was effective at eliminating MTAP-negative tumor cells, while providing protection to MTAP-positive healthy cells.

The 2FA+MTA combination successfully inhibited tumor growth in four different human tumor cell lines in mouse xenograft models. These results suggest that 2FA+MTA may be a promising drug combination, and that further testing is warranted.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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