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2012 Cancer Frontier Fund Award Recipients' Research Projects

Charitable gifts to The Foundation for Barnes-Jewish Hospital's Cancer Frontier Fund support innovative research projects at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. Together, we can unlock the mysteries of cancer and speed up the pace of turning discoveries into new tests, imaging technologies, drugs, vaccines and other therapies to help every patient survive his or her cancer; or to stop cancer before it starts.

Individual Awards

Targeting the bone marrow environment in Multiple Myeloma

Principal Investigator: Dan Link, MD

Multiple Myeloma is the second most common blood cancer; it is estimated that nearly 22,000 new cases will be diagnosed this year. Dr. Link’s project builds on observations made in his laboratory that treatment with a certain drug generates a 'toxic' environment for myeloma cancer cells in the bone marrow.

He will treat patients with multiple myeloma with this drug to determine if it improves their response to chemotherapy. If proven effective, this research may have applications for the treatment of other blood cell cancers, such as acute leukemia.

The neurobiology of chemotherapy induced Cognitive Impairment

Principal Investigator: Jay Piccirillo, MD, FACS

Approximately 20-30% of people who undergo chemotherapy experience some level of post-chemotherapy cognitive impairment. While any cancer patient may experience temporary cognitive impairment, long-term symptoms of PCCI are almost exclusively seen in patients treated for breast cancer, ovarian cancer, prostate cancer, and other cancers of the reproductive system.

Changes in memory, fluency, and other cognitive abilities impeded their ability to function as they had pre-chemotherapy. Using advanced neuroimaging techniques, Dr. Piccirillo and his colleagues will investigate whether chemotherapy affects neural connectivity within the brain.

Understanding mechanism of BRAF inhibitors in the induction of squamous cell carcinoma

Principal Investigator: Andrey Shaw, MD

Melanoma is one of the less common types of skin cancer, but causes the majority (75%) of skin cancer related deaths, an estimated 8,790 people in the US annually. If discovered early, it is highly treatable.

A promising new drug that inhibits melanoma growth has the unfortunate side effect of causing squamous cell carcinoma. This phenomenon substantially reduces the drug’s usefulness. Dr. Shaw proposes to use genome sequencing to understand why the drug causes squamous cell
tumors in hopes that this will to lead to better drugs for the treatment of melanoma.

MicroRNA expression signatures to predict Cervical Cancer outcome

Principal Investigator: Xiaowei Wang, PhD

Over 4,000 woman will die from cervical cancer each year in America. Most cervical cancer patients receive standard therapy; however, clinical outcomes vary significantly and are difficult to predict. This study focuses on discovering new molecular biomarkers for early identification of cervical cancer patients who would fail standard therapy. If patients could be identified this way, potential individualized therapies could be applied to these high-risk patients to improve treatment outcomes.

Team Awards

Exploring mechanisms of treatment resistance to improve outcomes in Pancreatic Cancer

Team Principals: David Linehan, MD; David DeNardo, PhD

Pancreatic cancer is highly resistant to chemotherapy; consequently, patient survival rates are extremely low, less than 3%. In this study, team members will test three unique hypotheses in hopes of determining why pancreas cancer is so resistant to chemotherapy.

By understanding the different biologic mechanisms by which cancer cells evade chemotherapy, we want to develop more effective strategies to overcome this resistance and improve patient outcomes.

Investigations of HER2 mutation in HER2 Negative Breast Cancer

Team Principals: Cynthia Ma, MD, PhD; Ron Bose, MD, PhD; Matthew Ellis, MB, PhD, FRCP; John Pfeifer, MD, PhD; and Feng Gao, MD, PhD

Recent declines in breast cancer mortality rates have been most significant among women with HER2-positive tumors, due in part to the widespread use of post-surgical hormone drug therapy. However, this treatment option is not FDA approved for use against HER2 negative cancer.
The Ma team is investigating a subset of HER2 negative breast cancer which carries an HER2 mutation that shows promise of responding to anti-HER2 drugs. If Dr. Ma and her team are successful in demonstrating this, better and more treatment options will become available for
patients with this type of breast cancer.

Validation of biomarkers for Kidney Cancer diagnosis and monitoring of Metastatic Disease

Team Principals: Jeremiah Morrissey, PhD; Evan D. Kharasch, MD, PhD; Vincent Mellnick, MD; Marilyn Siegel, MD; R. Sherburne Figenshau MD; Samuel Bhayani MD;Joel Picus, MD; and Jingqin Luo, PhD.

Kidney cancer represents about 3 percent of all cancers in the United States. Each year, more than 28,000 Americans are diagnosed with kidney cancer. Early diagnosis of kidney cancer dramatically increases the patient’s chance for survival; however, currently there is no screening
method for it.

Recently Dr. Morrissey discovered two urinary proteins that are clear indicators of kidney cancer. This study will determine if these biomarkers can correctly identify and predict cancerous kidney tumors, detect their spread to other parts of the body, and monitor the clinical effectiveness of patient treatment for metastatic disease.

Cancer immunotherapy targeting tumor-specific mutational antigens identified by exome sequencing

Team Principals: Robert Schreiber, PhD; William Gillanders, MD; Elaine Mardis, PhD; Eynav Klechevsky, PhD; Michael Welch, PhD; Ramaswammy Govindan, MD

Cancer genome sequencing can rapidly identify mutations in tumors. Some mutations function as tumor-specific antigens, stimulating the production of antibodies and thus targeting the tumor for destruction. This study seeks to extend and validate this observation and develop a method of rapidly and reliably identifying those tumor-specific antigens that most effectively induce immune system destruction of tumors to facilitate personalized immunotherapy for cancer.
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