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Stewardship Report Stewardship Report Presented to: The H Foundation December 2015 Our Appreciation Dear Friends of The H Foundation: The Robert H. Lurie Comprehensive Cancer Center of Northwestern University is deeply grateful for The H Foundation’s extraordinary support over the past 15 years. Since 2002, The H Foundation has raised and donated more than $3 million to advance research at the Lurie Cancer Center. In turn, the Lurie Cancer Center has been able to leverage these generous philanthropic funds into more than $50 million in private and government grants for cancer research projects that bridge basic science and clinical care. I am delighted to share this report featuring the faculty members who have received Bridge Awards, Pilot Awards, and other support during 2014-2015. Your giving continues to impact the investigations of our highly dedicated scientists as they work together to find a cure for cancer. Over the years, The H Foundation’s partnership has helped us to stimulate and enable creative, novel research that has led to fundamental new discoveries, accelerating progress towards achieving new diagnostics and treatments for cancer. At the Lurie Cancer Center, we are developing programs that bridge basic science and clinical care and that will establish Chicago as a global leader in the delivery of personalized cancer treatment. Established in 1974, the Lurie Cancer Center is recognized as one of just 45 National Cancer Institute (NCI)-designated “comprehensive” cancer centers in the country for its dedication to the highest standards of cancer research, patient care, education, and community outreach. Our center is a founding member of the National Comprehensive Cancer Network and the Big Ten Cancer Research Consortium. Through our affiliations with four Chicago hospitals, we treat more than 15,000 new cancer cases each year. The Lurie Cancer Center is enjoying remarkable growth, and we are so grateful to The H Foundation for its longstanding commitment. Your philanthropy is helping us to catalyze high-impact cancer studies and accelerate the pace of breakthroughs that will ultimately benefit patients for years to come. From the bottom of my heart, thank you again for your extraordinary dedication and support of our research efforts at the Lurie Cancer Center. Sincerely, Leonidas C. Platanias, MD, PhD Jesse, Sara, Andrew, Abigail, Benjamin and Elizabeth Lurie Professor of Oncology Director, Robert H. Lurie Comprehensive Cancer Center of Northwestern University 2 H Foundation Pipeline Awards 2014-2015 The H Foundation’s support helped to provide seed funds to promote early translational research. These funds are meant to support projects with innovative drug or product development ideas that would otherwise be difficult to fund because of early stage or lack of preliminary data. The following awards were bestowed in November 2014. Mary Hendrix, PhD President and Director, Stanley Manne Children’s Research Institute Professor, Robert H. Lurie Comprehensive Cancer Center of Northwestern University “Targeting nodal signaling in tumor cells to suppress aggressive cancer” The Centers for Disease Control and Prevention identify melanoma as the fastest growing cancer in the world. Metastatic melanoma is the leading cause of skin cancer deaths in the United States. Despite advances in the field, the reference therapy for patients diagnosed with metastatic melanoma is still the same chemotherapeutic agent that was first approved for treatment in the 1970’s, and is not effective in targeting drug resistant melanoma cells with stem cell properties. Therefore, to address a critical clinical need, Dr. Hendrix is performing a priority, proof-of-concept study with significant translational relevance for patients. The study is testing the effects of a newly developed and characterized 3D1 Nodal function-blocking monoclonal antibody as a therapy for metastatic melanoma, which will specifically target drug-resistant melanoma cells with stem cell properties that express Nodal. The results generated so far indicate that treatment of metastatic melanoma cells with the novel 3D1 antibody leads to suppression of tumor growth. In addition, Dr. Hendrix and her colleagues have developed the first detection assay for Nodal in patient blood samples, which will form the foundation for monitoring Nodal expressing cancers and selecting patients for Nodal-targeted therapy. The data generated from this innovative study will be used to support the rationale for bringing this therapy to an early phase clinical trial and to develop a diagnostic test to select melanoma patients who would benefit from anti-Nodal therapy. Dr. Hendrix and her team’s observations describing the translational potential of the 3D1 Nodal function-blocking monoclonal antibody will be published in the journal Oncotarget in 2015. Sui Huang, MD, PhD Associate Professor of Cell and Molecular Biology Richard Green, MD Professor of Medicine-Gastroenterology and Hepatology “Development of MEAN as an effective chemotherapeutic against hepatocellular carcinoma” Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide and is reaching epidemic proportions in the United States, with the incidence of HCC in America tripling over the past three decades. Since chemotherapy is relatively ineffective for HCC, the development of highly-effective and less toxic chemotherapeutic agents for HCC is essential to improving the survival of patients with this common, highly lethal form of cancer. Drs. Huang, Green, and their colleagues have recently developed a small molecule, 6-methoxyethylamino-numonafide (MEAN), which has shown to be effective against metastatic tumor markers in mice. It has high potential as a candidate for further development into an anti-HCC chemotherapeutic drug. This study aims to further develop MEAN to make it Investigational New Drug (IND)–ready. 3 In addition to the studies accomplished with funds from The H Foundation, Drs. Huang and Green have made further progress comparing the anti-tumor growth properties of MEAN with sorafenib, the only FDA-approved drug against hepatocellular carcinoma. A manuscript describing their findings is currently in review for publication. Teresa K. Woodruff, PhD Director, Women’s Health Research Institute; Chief, Division of Obstetrics and Gynecology-Fertility Preservation; Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology; Professor in Obstetrics and Gynecology-Fertility Preservation, McCormick School of Engineering, Medical Social Sciences and Medicine-Endocrinology “Activin antagonists for treatment of cachexia” Half of all patients with cancer lose some body weight, with up to 30 percent of all cancer deaths being related to significant cancer-related cachexia and muscle wasting. Cachexia is known as general physical wasting with loss of weight and muscle mass due to a disease. Cancer-related cachexia is a major concern in the management of most late-stage cancers and is the acute cause of death in many of these patients. Because activin is one of the molecules that drives muscle wasting, a focused effort on the development of a small molecule antagonist of activin signaling is a vitally important endeavor. This project aimed to develop new sets of drug-like activin antagonists to make these suitable for subsequent development into pre-clinical leads. The novel compounds that Dr. Woodruff and her group synthesized through The H Foundation pipeline award were a critical component of an invention disclosure that was recently submitted to Northwestern University as the first step towards patenting this class of molecules. This new intellectual property will give our scientists a greater chance of partnering with external organizations, such as pharmaceutical companies, who can help drive our discoveries towards the clinic. The group’s efforts to screen and test compounds led to a publication in the Journal of Medicinal Chemistry. In addition, Dr. Woodruff submitted a National Institutes of Health grant application this past June to continue supporting this work. Dr. Woodruff and her colleagues continue to test the new compounds. Their hope is to identify one or more compounds, which have suitable characteristics for testing in animal models of cancer cachexia. Leonidas C. Platanias, MD, PhD Jessica Altman, MD Associate Professor of Medicine-Hematology/Oncology “Optimization of Mnk-eIF4E inhibitors for the treatment of malignancies” Acute myeloid leukemia is a very heterogeneous disease with many patients facing a poor outcome—especially those who cannot tolerate high-dose chemotherapy. Drs. Platanias and Altman’s work is focused on developing new therapeutic strategies for myeloid leukemias that can enhance clinical outcomes in patients. Specifically, their laboratory has shown that chemotherapy as well as mTOR inhibitors can induce the MNK pathway, which allows the leukemia cells to continue to proliferate. Therefore, targeting of the MNK pathway is important in order to prevent relapse and/or resistance to current therapies in leukemia patients. Drs. Platanias and Altman have been working with the Medicinal Chemistry and High Throughput Analysis Laboratory cores at Northwestern to identify Mnk1 inhibitor compounds and then modify them with the goal of developing drugs that can be advanced into the clinic. They have identified several new inhibitors and have synthesized many new compounds in 4 their preliminary hit-to-lead optimization. The funds from The H Foundation were used to improve the potency and drug-like
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