Biomarker for aggressive, basal-like breast cancer identified

A biomarker strongly associated with basal-like breast cancer has been identified. Basal-like breast cancer is a highly aggressive carcinoma that is resistant to many types of chemotherapy. The biomarker, STAT3 protein, provides a smart target for new therapeutics designed to treat this often deadly cancer.

Using breast cancer patient data taken from The Cancer Genome Atlas, molecular biologists Curt M. Horvath, PhD, and Robert W. Tell, PhD, both of Northwestern University in Evanston, Illinois, used powerful 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," Horvath said. "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 were published in the Proceedings of the National Academy of Sciences (2014; doi:10.1073/pnas.1404881111).

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. This research is the first reported study to compare breast cancer subtypes and gene expression patterns associated with STAT3 in the tumors of human patients.

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.

"The Cancer Genome Atlas is a really rich and growing database of publicly available data created to help us understand cancer," said Horvath, who is a program co-leader of the Signal Transduction in Cancer program at the Lurie Cancer Center. "It allows basic scientists to ask interesting questions about cancer and contribute to clinical care."

Horvath and Tell observed that there are many clearly visible patterns of common gene expression—where certain genes are turned on and certain genes are turned off—in the basal-like cancers. Those clear patterns were not seen in the luminal cancers.

"This opens up the possibility that cancer subtype-specific signaling is driven by STAT3 and that STAT3 inhibitors may be more effective in patients diagnosed with basal-like cancers than in those with luminal cancers," Horvath said.

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