Overactive protein viewed as a smart target for novel therapeutics

Scientists at Northwestern University have identified a biomarker strongly associated with basal-like breast cancer, an aggressive carcinoma that is resistant to many types of chemotherapy. The biomarker, a protein called STAT3, provides a smart target for new therapeutics designed to treat this often deadly cancer, according to the researchers.

Using breast cancer patient data taken from The Cancer Genome Atlas, Curt M. Horvath, Ph.D., and Robert W. Tel, Ph.D., used computational and bioinformatics techniques to detect patterns of gene expression in two cancer subtypes. They found that a small number of genes are activated by STAT3 protein signaling in basal-like breast cancers but not in luminal breast cancers.

Basal-like cancer is a category that includes a number of different breast cancers, including the highly aggressive form called triple negative cancer.

“You can't treat breast cancer as one disease,” said Dr. Horvath. “Cancer describes many molecular processes that have gone wrong. We have teased out from large amounts of data that STAT3 activity correlates with distinct patterns of gene expression in one type of breast cancer but not in another.”

The findings (“Bioinformatic analysis reveals a pattern of STAT3-associated gene expression specific to basal-like breast cancers in human tumors”) are published in the online early edition of the journal Proceedings of the National Academy of Sciences. The results suggest a clinical study should be conducted of a STAT3-inhibiting drug in patients with basal-like and luminal cancers, Horvath said. Currently there are no pills or injections targeting STAT3 for breast cancer patients.

Previous research has found the STAT3 protein to be overactive in many breast cancers, but its role has not been well understood. Drs. Horvath and Tell's research is the first reported study to compare breast cancer subtypes and gene expression patterns associated with STAT3 in the tumors of human patients.

“[Our] results indicate clearly identifiable STAT3-regulated signatures common to basal-like breast cancers but not to luminal A or luminal B cancers. Furthermore, these differentially expressed genes are associated with immune signaling and inflammation, a known phenotype of basal-like cancers,” wrote the investigators.

“These findings demonstrate a distinct role for STAT3 signaling in basal breast cancers, and underscore the importance of considering subtype-specific molecular pathways that contribute to tissue-specific cancers.”

Dr. Horvath emphasized that this is a statistical analysis and the findings need to be verified with careful laboratory and clinical experiments. He plans to conduct such a study with colleagues at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

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