Scientist Identifies Triple-Negative Breast Cancer Target for Drug Development

FDA-Approved Drug Curbs Tumor Growth in Mouse Model for Deadly Form of Breast Cancer

By Jeffrey Norris    |   UCSF.edu | October 3, 2013

Scientist Identifies Triple-Negative Breast Cancer Target for Drug Development

Luika Timmerman, PhD, showed that growth of about one-third of triple-negative
breast cancers overproduce a cell-surface protein called xCT (green), which she targeted with an FDA-approved drug to slow tumor growth.

Often deadly "triple-negative" breast cancers might be effectively treated in many cases with a drug that targets a previously unknown vulnerability in the tumors, according to a new UC San Francisco study.

UCSF researcher Luika Timmerman, PhD, an investigator in the UCSF Helen Diller Family Comprehensive Cancer Center, found that many cell lines obtained from triple-negative breast cancer are especially dependent on cystine, one of the 20 amino acids that are the building blocks of proteins that all cells need. She used an FDA-approved drug to inhibit activity of a transporter protein that ferries cystine into triple-negative breast cancer cells, and found that it significantly inhibited their growth in culture and when the cancer cells were transplanted into mice.

Timmerman described her discovery in a study published online on Oct. 3  in the journal Cancer Cell.

Difficulty of Treating Triple-Negative Breast Cancer

Roughly one in six women with breast cancer have triple-negative breast cancer, and only about three out of four with this type survive five years or more. These tumors sometimes grow aggressively, advancing from being undetectable to becoming difficult-to-treat between regular screening mammography exams, for instance.

Drugs now are available that effectively target the estrogen and HER2 receptor proteins, which are found in many breast tumors, and these drugs spare most normal cells in the body.

However, triple-negative breast cancers are difficult to treat effectively because they do not make either of these receptors. To treat patients with triple-negative breast cancer, physicians instead use older chemotherapies that produce side effects in normal tissues, thus limiting the doses that patients can receive.

Timmerman found that she could significantly slow growth of triple-negative tumors using an FDA-approved anti-inflammatory drug called sulfasalazine to block a specific cystine transporter called xCT. While sulfasalazine itself would not be appropriate for treating cancer, Timmerman said, it could serve as a "lead compound" that could be used to develop drugs that specifically target xCT on tumor cells.

"This study of human tumors in mice and of breast cancer cell lines demonstrates the potential of targeting not only this cystine transporter, but also other metabolic abnormalities in cancer," Timmerman said.

 

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