Clinical Implications

New Agent May Control Breast Cancer Growth and Spread

Carlo CroceA study led by researchers at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) suggests an experimental drug can slow breast-cancer aggressiveness, reverse resistance to the drug fulvestrant and maybe improve efficacy of other breast-cancer drugs.

Findings from the laboratory and animal study might offer a new strategy for treating breast cancer. The drug, called AS1411, belongs to a class of agents called G-rich aptamers. It works by blocking the cell’s production of microRNA, molecules that help cells control the amount and kinds of proteins they make. Abnormal levels of certain microRNAs are a hallmark of many cancers.

Specifically, the drug inhibits a protein called nucleolin that plays a critical role in the microRNA maturation process.

“This study of the role of nucleolin in microRNA regulation has clear clinical implications,” says principal investigator Carlo Croce, MD, director of Human Cancer Genetics at Ohio State and a member of the Molecular Biology and Cancer Genetics Program (MBCG) at the OSUCCC – James.

“It supports a novel treatment for breast cancer that reduces cancer aggressiveness and restores drug sensitivity by inhibiting the processing of specific microRNAs that are highly expressed in cancers.”

First author Flavia Pichiorri, PhD, assistant professor of Hematology and also a member of the MBCG Program, notes that nucleolin is a promising therapeutic target for microRNA modulation in cancer cells.

“To our knowledge, this is the first large study to show a clear association between nucleolin and specific microRNAs that are causally involved in cancer,” Pichiorri says. “We also believe it’s the first study to show that targeting nucleolin with a G-rich aptamer can control breast-cancer metastasis in an animal model through microRNA regulation.”

Published in the Journal of Experimental Medicine.

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