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The fact that cancer cells have an altered glucose metabolism, has sparked new interested in the pharmaceutical industry in it’s continuous quest of finding new ways to target tumors. Reversing the increased glucose consumption in cancer cells is an important step and has great potential for therapeutic drug developments. This meeting is designed to shed light on current strategies of how to change the metabolism in cancer cells and the resulting opportunities for developing new molecular drug targets.
WEDNESDAY, NOVEMBER 2
7:00 am Conference Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
8:40 Malic Enzyme 2 (ME2) as a Novel Cancer Metabolic Target
Vikas Sukhatme, Professor, Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School
We have discovered that ME2 is widely overexpressed in a number of tumor types. Its inhibition can decrease tumor growth and induce differentiation in vitro and in vivo.
9:10 Targeting Atypical Glucose Transporter Regulation in Multiple Myeloma with HIV Protease Inhibitors
Mala Shanmugam, Ph.D., Research Assistant Professor , Robert H.Lurie Comprehensive Cancer Center, Northwestern University
Tumor cells, including the fatal B cell malignancy multiple myeloma, consume surprisingly high amounts of glucose. While elevated glucose utilization forms the basis for clinical imaging of various cancers, we are not yet able to target glucose utilization for therapy. We have identified a subset of glucose transporters (GLUTs) that are uniquely regulated in myeloma including the insulin-responsive glucose transporter GLUT4, providing targeting opportunities selective to these tumor cells. In addition we have identified an FDA approved HIV protease inhibitor that has an off-target effect on GLUT4, warranting repositioning of this class of compounds for the treatment of GLUT4-dependent cancers. Our studies range from target identification, in vitro cell line validation and ex vivo pre-clinical studies in myeloma patient samples providing novel approaches to treat this incurable cancer.
9:40 Targeting Carbonic Anydrases IX and XII, Regulators of Cellular pH in Hypoxia
Shoukat Dedhar, Ph.D., Professor, Distinguished Scientist, University of British Columbia and BC Cancer Research Centre, Vancouver
Carbonic Anhydrase IX ( CAIX) is a hypoxia inducible protein that regulates intra- and extra-cellular pH under hypoxic conditions and promotes tumor cell survival and invasion in hypoxic microenvironments. CAIX is specifically expressed in aggressive triple-negative and basal type breast tumors and is a poor patient prognostic marker. We have targeted CAIX with novel small molecule inhibitors and have shown that CAIX inhibitions results in significant growth delay of orthotopic breast tumors, and also in significant inhibition of lung metastasis formation. New data on the role of CAIX in cancer stem cells will be discussed.
10:10 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:40 Talk Title to be Announced
Kate Yen, Ph.D., Associate Director, Biology, Agios Pharmaceuticals, Inc.
11:10 Sponsored Presentations (Opportunities Available)
11:40 Targeting the Warburg Effect by Synthetic Lethality
Ray Tabibiazar, M.D., CEO, Ruga Corporation
Paul Pearson, Ph.D., VP, Pre-Clinical Development, Ruga Corporation
Identifying new molecular targeted therapies that specifically kill tumor cells while sparing normal tissue is the next major challenge of cancer research. We describe here strategies to target the Warburg Effect in a genetically defined patient population by utilizing synthetic lethality.
12:10 pm Interfering with Cancer Cell Signaling
Speaker to be Announced
12:40 Luncheon Presentation
tONCO™: Taconic’s Innovative Portfolio of Tools and Capabilities to Evaluate the Efficacy of Novel Cancer Therapeutics
David S. Grass, Ph.D., Vice President, Scientific Operations, Taconic
Taconic’s tONCO™ Platform encompasses several tools and services designed to facilitate the preclinical assessment of novel cancer therapeutics. Among the approaches, an in vivo and ex vivo bioluminescent imaging platform to evaluate compound efficacy has been developed. In these mouse models, xenograft orthotopic tumor grafts are being used that are more relevant with respect to host-tumor interactions, display metastatic potential and allow the evaluation of responses to novel therapeutics. These models take advantage of Taconic’s extensive suite of immunodeficient mouse strains and allow for the quantitative analysis and high throughput in vivo assessment of potential anti-tumor and anti metastatic activity.
2:20 Chairperson’s Remarks
2:25 Conserved Features of Cancer Cells Define their Sensitivity of HAMLET-Induced Death; C-Myc and the Warburg Effect
Petter Storm, Scientist, Laboratory Medicine, Microbiology, Immunology and Glycobiology (MIG), Lund University
HAMLET is the first member of a new family of tumoricidal protein-lipid complexes, and has shown great promise as a human drug candidate, with therapeutic efficacy against skin papillomas and rapid topical effects on human bladder cancers. The results of our research identify HAMLET as a novel anti-cancer agent that exploits unifying features of cancer cells for its activity, including c-Myc and the shift in glycolysis known as the ’’Warburg effect’’.
2:55 Targeting Mitochondria for Cancer Therapy :Role of Mitochondrial Hexokinase in Prevention of Apoptosis
Charles Wenner, Ph.D., Member, Department of Cell and Molecular Biology, Roswell Park Cancer Institute
Description-Historical perspective of the Warburg Effect with emphasis on modulation of high glycolytic rates in rapidly growing tumor cells for therapy. The need for a re-examination of the specific contributions of mitochondrial hexokinases and glucose metabolism is discussed in view of demonstrations that these hexokinases can antagonize apoptosis downstream of Bax activation despite metabolic disruption which suggests that metabolism per se is not obligatory for this process. These findings suggest that new approaches of targeting apoptotic susceptibility may be conceived.
3:25 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
4:05 Development of Chemical Probes to Study Cancer Metabolic Reprogramming
Sergey A. Kozmin, Ph.D., Associate Professor, Chemistry, University of Chicago
Understanding of the nature of reprogrammed energy metabolism in cancer cells is of significant current interest. We will describe the development of an arsenal of new small-molecule probes to study altered energy metabolism in cancer. This study is aimed at identifying the underlying reasons for major alterations in energy producing pathways employed by rapidly proliferating cells and testing the possibility of targeting such cells in vitro and in vivo.
4:35 Potent Anti-Cancer Lipoate Analogs Selectively Attack Tumor Cell Mitochondrial Metabolism
Paul Bingham, Ph.D., Vice President, Research, Cornerstone Pharmaceuticals
Among the enzymes whose regulation is reprogrammed in many tumor cells is the pyruvate dehydrogenase complex (PDH). The lipoate moieties of PDH serve both catalytic and regulatory function. Non-redox active lipoate analogs apparently attack cancers-specific elements of this lipoate-sensitive regulatory apparatus, causing cancer cell death in cell culture and in human tumor xenograft models.
5:05 Interactive Breakout Discussion Groups
6:15 – 7:15 Welcoming Reception in the Exhibit Hall with Poster Viewing
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