Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine: Leading the Way in Cancer Genomics

Laura Bruck | September 07, 2012
Siteman Cancer Center

Siteman Cancer Center

An international leader in cancer treatment, research, prevention, education, and community outreach, the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, Missouri, is the only cancer center in the state (and within a 240-mile radius of St. Louis) to be designated a Comprehensive Cancer Center by the National Cancer Institute, and to serve as a member of the National Comprehensive Cancer Network.

With more than 350 Washington University researchers and physicians providing care for over 8000 newly diagnosed patients each year, Siteman is consistently ranked among the nation’s best cancer centers by US News & World Report. It provides a full range of advanced diagnostic and therapeutic services for patients with all types of cancer, many in the state-of-the-art Center for Advanced Medicine (CAM), an outpatient facility that opened on the Barnes-Jewish Hospital campus in 2001.

Siteman patients have access to more than 250 therapeutic clinical trials, and Siteman-affiliated scientists and physicians hold more than $165 million in annual cancer research and related training grants. Two such grants, from Susan G. Komen for the Cure, were uncharacteristically awarded to scientists from the same institution, namely Washington University, in 2 consecutive years—one to research prevention of late breast cancer relapse and the other to investigate breast cancer vaccine therapy.

This research would not be possible if not for the large-scale DNA sequencing and analysis provided by geneticists Richard K. Wilson, PhD, Elaine Mardis, PhD, and Timothy Ley, MD, at The Genome Institute at Washington University. As leaders in cancer genomics, Siteman/Washington University scientists were the first to sequence and comparatively analyze a tumor and normal genome from a cancer patient, a woman with acute myeloid leukemia. They have performed similar studies in breast cancer and, in a groundbreaking study reported in Nature,1 have sequenced 46 breast cancer tumor/normal pairs. To date, Institute scientists have sequenced the genomes of tumor cells from more than 700 cancer patients. Based on the information gleaned from this whole-genome sequencing, researchers are beginning to reclassify tumors based on their genetic makeup rather than their location, ushering in a new era in personalized medicine.

Dr. Matthew Ellis

Matthew Ellis, MB, BChir, PhD

ER-Positive Disease: Preventing Late Relapse

In May 2012, oncologist and professor of Medicine at Washington University School of Medicine Matthew Ellis, MB, BChir, PhD, along with Pascal Meier, PhD, (The Institute of Cancer Research in London) and Mardis, was awarded a 5-year, $4 million Susan G. Komen for the Cure grant to investigate cell death activation to prevent late relapse in estrogen receptor (ER)–positive breast cancer.

The high prevalence of late relapse of ER-positive breast cancer can be attributed to the huge variations in efficacy of endocrine therapy. “Tumor growth may be reduced, but in many cases, cells survive and proliferate, and a woman who does fine for 5 or even 10 years can then suffer a systemic relapse,” said Ellis, noting that once this occurs, ER-positive disease produces a chronic debilitating illness that is uniformly fatal.

Working from the premise that “abnormal cell survival mechanisms in ER-positive disease that allow recurrence after 5 years can be targeted with carefully chosen experimental drugs that cause tumors to regress completely,” Ellis and colleagues are taking advantage of the new technology that has enabled identification of the differences in the DNA sequences between normal and ER-positive cancer cells. The team began by examining the pattern of these DNA changes to better understand the causes of late relapse and more accurately predict which patients are at high versus low risk, with the aim of developing precise therapeutic solutions for high-risk patients.

“Whole-genome sequencing permits a completely unbiased approach,” Ellis said. “Using the information we obtain, we plan to expand the number of cases sequenced to nearly 3000 to see if we can build better models for endocrine therapy resistance and relapse risk.”


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