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Pathways to Discovery: Winter 2012

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Gene Test May Predict Breast Cancer Response to Treatment

If we knew [who would respond] in advance, we could find the best treatment for each patient.
Ralph Weichselbaum, MD

A new gene signature test being developed at UChicago has the potential to take some of the guesswork out of breast cancer treatment.

The challenge with current standard treatment lies in identifying which patients with breast cancer will benefit from standard radiation therapy or chemotherapy.

"If we knew that in advance, we could find the best treatment for each patient," said Ralph Weichselbaum, MD, chair and D.K. Ludwig Professor of Radiation & Cellular Oncology, who, with his colleagues, found a gene signature that is associated with chemotherapy and radiation resistance.

The discovery is so exciting that The University of Chicago Office of Technology and Intellectual Property (UChicagoTech) is funding research to validate the gene signature with a $50,000 grant through the Innovation Fund, which was set up to support proof-of-concept projects that could potentially be licensed for commercial use.

Genes in Common
For more than 7 years, Dr. Weichselbaum and colleagues have been studying how tumor cells become resistant to radiation therapy and chemotherapy, and whether resistance is related to how tumor cells spread in the body.

When they compared genes found in tumor cells resistant to radiation with those in tumor cells that are responsive to radiation, they discovered 50 genes that were differentially expressed. Twenty-four of the genes were part of the interferon pathway. Interferons are proteins made and released by host cells in response to the presence of foreign invaders, such as viruses.

The research group, led by Nikolai Khodarev, PhD, associate professor of radiation and cellular oncology, further investigated this finding by suppressing the interferon signaling pathway. As a result, cells became sensitive to the effects of radiation and the chemotherapeutic agent doxorubicin, showing that the genes had the ability to control resistance to therapy.

Another group, led by Andy Minn, MD, PhD, now an assistant professor of radiation oncology at the University of Pennsylvania, discovered that expression of genes in the interferon pathway is found in many common human cancers, including breast cancer.

By using only seven genes in the interferon pathway signature, a classifier was developed and tested on multiple datasets from breast cancer patients to determine if the classifier could identify which patients would respond to chemotherapy and radiation. Analysis revealed that women who did not respond to radiation therapy and suffered local recurrences of cancer in the breast, chest wall, or regional lymph nodes were more likely to express the seven-gene signature. Similarly, the classifier also predicted which patients would benefit from chemotherapy to prevent metastasis.

UChicagoTech is working with Dr. Weichselbaum to advance the test, which could one day optimize breast cancer treatment.

"We're hoping we can develop a reproducible clinical test and verify it in a large cohort," Dr. Weichselbaum said.

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