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About This Conference:

It has been known for decades that the glucose consumption of cancer cells is greater than that of non-malignant cells due to a higher rate of glycolysis in the tumor cell. Inhibition of glycolytic energy production is providing the framework for the discovery of new anti-cancer compounds. This meeting will cover the progress of therapeutic agents against these newer cancer targets, discuss the latest findings that are influencing their development and highlight newer metabolism-related cancer targets.


Thursday, October 9

11:30 am Registration


1:00 pm Plenary Keynote Program 
 

Chas BountraChas Bountra, Ph.D., Professor of Translational Medicine & Head, Structural Genomics Consortium, University of Oxford

Martin TolarMartin Tolar, M.D., Ph.D., Founder, President & CEO, Alzheon, Inc.

Andrew L. Hopkins, Andrew L. Hopkins, D.Phil, FRSC, FSB, Chair of Medicinal Informatics and SULSA Research Professor of Translational Biology, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee


2:45 Refreshment Break in the Exhibit Hall with Poster Viewing


ONCO-METABOLIC CANDIDATES IN DEVELOPMENT

3:45 Chairperson’s Opening Remarks

Marcia Haigis, Ph.D., Associate Professor, Department of Cell Biology, Harvard Medical School

3:55 FEATURED PRESENTATION: Drugging Mutant IDH at the Crossroads of Cancer and 2HG Aciduria

Lenny DangLenny Dang, Ph.D., Senior Director, Biochemistry, Agios Pharmaceuticals, Inc.

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We previously demonstrated recurrent IDH mutations found in low-grade glioma, AML and cholangiocarcinoma produce the oncometabolite 2-hydroxyglutarate (2HG) leading to impaired histone methylation and a block in differentiation. Interestingly, D-2HG is also pathogenic for the rare and devastating D-2HG aciduria. We have developed selective potent inhibitors against mutant IDH1 & IDH2 for the treatment of 2HG-driven diseases. These drug candidates have just entered clinical trials.

4:25 Inhibition of Glucose Uptake by PFK-158, a Novel Anti-Cancer Agent

Gilles Tapolsky, Ph.D., CSO, Advanced Cancer Therapeutics

4:55 Challenges and Insights for Monitoring and Measuring Cancer Metabolomics

Alexander M. Buko, Ph.D., Vice President, Business and Product Development, Human Metabolome Technologies America

Cancer is a disease that is frequently defined by an altered cellular metabolism, therefore, metabolomics can play a major role in early detection and diagnosis and in the evaluation of medical interventions and therapies. HMT performs quantitative metabolite profiling in combination with statistical informatics and pathway analysis to perform metabolite measurements and biomarker discovery. We will discuss HMT applications in Pre-clinical and Clinical studies. 

5:25 Coffee Break in the Foyer

5:40 CPI-613’s Two-Pronged Attack on Glucose Metabolism and Tumor Growth

Paul Bingham, Ph.D., Associate Professor, Department of Biochemistry and Cell Biology, Stony Brook University and Vice President Research, Cornerstone Pharmaceuticals

Attacking altered mitochondrial metabolism is a potent approach to cancer chemotherapy. Lipoate plays a central role in regulating tumor-specific mitochondrial energy flows. We have pioneered the use of lipoate analogs to target tumor metabolism with power and selectivity. I will discuss new progress in understanding both the fundamental mechanism of action and the clinical performance of these first-in-class agents.

6:10 Discovery and Development of CB-839, a Glutaminase Inhibitor that Targets Tumor-Specific Metabolism

Francesco Parlati, Ph.D., Director, Department of Biology, Calithera Biosciences

6:40 Close of Day

7:00 Dinner Short Courses*

*Separate registration required


Friday, October 10

7:30 am Registration


8:00 Interactive Breakfast Breakout Discussion Groups

This interactive session provides conference delegates and speakers an opportunity to choose a specific roundtable discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Epigenetics and Cancer Metabolism

Udo Oppermann, Ph.D., Professor and Principal Investigator, Structural Genomics Consortium, Oxford University

• What is the connection between cancer metabolism and epigenetics?
• Which epigenetic modifications are the most disregulated/altered in specific cancers?
• Which oncogenes are disregulated by epigenetic modifications and what are the therapeutic intervention points?Which onco-genes are disregulated by epigenetic modifications and what are therapeutic intervention points? What is the current state of therapeutically modulating epigenetic regulators involved in altered cancer metabolism?

Cell cycle control and Cancer Metabolism

Lluis Fajas, Ph.D., Professor and Director, Physiology, University of Lausanne

• Where are the connections?
• What to target for drug discovery?
• Can current therapies or drug in development be repurposed with new ‘cell cycle’ knowledge?

Development Challenges for potential Cancer Metabolic Therapies

Paul Bingham, Ph.D., Associate Professor, Department of Biochemistry and Cell Biology, Stony Brook University and Vice President Research, Cornerstone Pharmaceuticals

• New assays, cell lines and animal models
• Tumor imaging
• Combination therapies


CELLULAR METABOLISM AND CANCER TARGETS

9:00 Chairperson’s Remarks

Francesco Parlati, Ph.D., Director, Department of Biology, Calithera Biosciences

9:10 New Insights in Tumor Metabolism: Lessons Learned from Sirtuins

Marcia Haigis, Ph.D., Associate Professor, Department of Cell Biology, Harvard Medical School

Tumor cells redirect metabolism of fuels in order to meet their demands for energy, stress responses and generation of anabolic metabolites needed for rapid proliferation. Understanding how mitochondria contribute to tumorigenesis and emerging therapeutic resistance is a major focus in cancer biology. Mitochondrial sirtuins are NAD-dependent enzymes that post-translationally modify enzymes involved in metabolism and stress responses. Here we will discuss how mitochondrial acetylation impacts cell survival and growth. A better understanding of sirtuin-mediated regulation may identify novel ways to therapeutically target diseases associated with aging, such as cancer.

9:40 Metabolic Regulation of Stem-like Cancer Cells through AKT Activation and Therapeutic Implications

Peng Huang, M.D., Ph.D., Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center

This presentation will focus on the regulation of stem-like cancer cells (side population, or SP cells) by glucose, a key metabolic substrate in generation of cellular energy and metabolic intermediates for cell proliferation. The potential mechanisms involved in this metabolic regulation of SP cells will be discussed. A potential therapeutic strategy to target this process and kill cancer stem cells will also be presented.

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:55 Identifying Metabolic Dependencies in Pancreatic Cancer

Alec Kimmelman, M.D., Ph.D., Assistant Professor, Dana Farber Cancer Institute, Harvard Medical School

Our work has shown that pancreatic cancers have an altered cellular metabolism. We have demonstrated that in many cases, oncogenic Kras plays a key role in regulating the metabolism of this tumor type. Importantly, several of these metabolic pathways are critical for tumor growth and therefore represent potential therapeutic targets. These and other aspects of pancreatic cancer metabolism will be discussed.

11:25 Cell Cycle Regulators Link Metabolism and Proliferation in Cancer Cells

Lluis Fajas, Ph.D., Professor and Director, Physiology, University of Lausanne

Analysis of genetically engineered mice deficient for cell cycle regulators, including E2F1, cdk4, or, pRB showed that the major phenotypes are metabolic perturbations. We proved that these key cell cycle regulators contribute to lipid synthesis, glucose production, insulin secretion, and oxidative metabolism and how deregulation of those pathways can lead to metabolic perturbations. These examples illustrate the growing notion that cell cycle regulatory proteins can also modulate metabolic processes.

11:55 mTOR/S6K Pathway-Dependent Metabolic Reprogramming in Cancer Cells Mediates Resistance to Glycolytic Inhibitors

Raju Pusapati, Ph.D., Postdoctoral Research Fellow, Discovery Oncology (Jeff Settleman Lab), Genentech, Inc.

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Although the targeting of “glycolytic addiction” offers tremendous potential in cancer therapy, it has not been successful in the clinic thus far. Our work attempts at understanding the underlying mechanisms by which cancer cells escape glycolytic dependency. Employing a combination of metabolomic and biochemical approaches we tease out the metabolic and signaling pathways that underlie cancer cell resistance to glycolytic drugs.

12:25 pm Metabolic Reprogramming of Myc- dependencies by a Histone Demethylase Inhibitor

Udo Oppermann, Ph.D., Professor and Principal Investigator, Structural Genomics Consortium, Oxford University

The reversible N-epsilon methylation of lysyl residues in chromatin proteins plays an important role in gene regulation and chromatin stability. Here we show that a recently developed histone demethylase inhibitor induces specific pro-apoptotic signatures and stress responses in Myc-dependent malignancies which is caused by a metabolic reprogramming of cancer cells.

12:55 Session Break

1:05 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:45 Session Break


METABOLISM, METASTASIS, MITOCHONDRIA, MORE TARGETS

1:55 Chairperson’s Remarks

Raju Pusapati, Ph.D., Post-Doctoral Research Fellow, Discovery Oncology (Jeff Settleman Lab), Genentech, Inc.

2:00 Mitochondrial Complex 1 Dysfunction and Cancer

Ivana Kurelac, Ph.D., Postdoctoral Fellow, Genetics Unit, University of Bologna

Respiratory complex I (CI) has shown to be essential for the induction of Warburg effect and adaptation to hypoxia of cancer cells, allowing them to sustain tumor growth. The mechanistic link between CI and Warburg effect will be discussed, together with how different CI defects may lead to opposite effects on tumor growth, introducing thus a novel cancer gene definition of oncojanus.

2:30 Targeting Energy Metabolism for Brain Cancer

Purna Mukherjee, Ph.D., Research Assistant Professor, Department of Biology, Boston College

Emerging evidence indicates that cancer is primarily a metabolic disease arising from defects in cell mitochondria. In contrast to normal neurons and glia, which transition to ketone bodies for respiratory energy when glucose levels are reduced, malignant brain tumors are mostly dependent on non-oxidative substrate level phosphorylation. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and metabolically challenged tumor cells. This metabolic approach to brain cancer management is supported from case studies in patients and orthotopic syngeneic models.

3:00 Refreshment Break in the Exhibit Hall with Poster Viewing

3:30 Physiological and Oncogenic Regulation of Nucleotide Biosynthesis

Issam Ben-Sahra, Ph.D., Senior Fellow, Laboratory of Brendan Manning, Oncology, Harvard Medical School

The mechanistic target of rapamycin (mTOR), as part of mTORC1, is a protein kinase that senses growth signals to regulate anabolic growth and proliferation. We found that activation of mTORC1 leads to the acute stimulation of metabolic flux through the de novopyrimidine synthesis pathway. I will discuss a new mechanism of regulation of nucleotide synthesis by mTORC1 signaling in response to growth and oncogenic signals.

4:00 Serine Catabolism and Mitochondrial Redox Control

Jiangbin Ye, Ph.D., Research Scholar, Thompson Lab, Memorial Sloan-Kettering Cancer Center

The de novo synthesis of the non-essential amino acid serine is often upregulated in cancer. We demonstrate that mitochondrial serine hydroxymethyltransferase (SHMT2) is induced when Myc-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the catabolism of serine, resulting in net production of NADPH, which is critical for maintaining redox balance and cell survival under hypoxia.

4:30 New Inhibitors for Lactate Dehydrogenase A 

Marie Evangelista, Ph.D., Scientist, Discovery Oncology, Genentech Inc.

GNE-140 is a novel small molecule inhibitor targeting LDHA, an enzyme which catalyzes the conversion of pyruvate to lactate in the last step of glycolysis. Pharmacogenomic profiling of ~400 tumor cell lines with GNE-140 identified subsets (~15%) of glycolytically-dependent cell lines.  Despite the metabolic plasticity of cells, the timing of acquired resistance to GNE-140 was comparable with other targeted agents.  Under long-term treatment with GNE-140, glycolytic cells acquired resistance by increased oxidative phosporylation (OX-PHOS) in a mechanism dependent on the AMPK stress response pathway; targeting either AMPK, downstream kinases, or OX-PHOS using tool compounds synergized with and prevented acquired resistance to GNE-140.  Our data suggests that targeting aerobic glycolysis may benefit a subset of patients and that combinations with agents that block AMPK signaling or the mitochondria will be effective at delaying tumor relapse.     
 

5:00 Close of Conference

 

Suggested Event Package:

October 7 Short Course: Targeting Protein-Protein Interactions 

October 7 Short Course: Introduction to Targeted Covalent Inhibitors 

October 8-9: Protein-Protein Interactions as Drug Targets Conference 

October 9-10: Cancer Metabolism

October 9 Dinner Course: Integration of BDDCS and Extended Clearance Principles for Understanding Disposition and ADME liabilities or Introduction to Drug Metabolism 


*Separate registration is required


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PREMIER SPONSOR 

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SPONSORSHIPS & EXHIBITS 

The exhibit hall was sold out in 2013, so please contact us early to reserve your place. To customize your sponsorship or exhibit package for 2014, contact:

Jon Stroup
Business Development Manager
781-972-5483
jstroup@healthtech.com 

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