The science of cancer stem cells is still evolving, and despite the many unknowns, holds significant promise for the next phase of oncology therapeutics. The Targeting Cancer Stem Cells in Oncology Symposium is a new addition to the 2012 Molecular Medicine Tri-Conference, and reflects the growing interest in Cancer Stem Cells (CSCs) and their associate pathways in Pharma and Biotech as oncology drug targets. This symposium will feature case studies from scientists working with the unique challenges presented by cancer stem cells, from isolation and characterization of cell lines to the development of screening assays and pre-clinical models. The origin of cancer stem cells, and their role in treatment resistance and recurrence will be discussed. Sessions will also highlight some of the novel cancer stem cell therapeutic development programs and platforms. An interactive format will enable open discussion to address many of the questions the field’s leading researchers are striving to answer.
RECOMMENDED SHORT COURSES*:
*Separate registration required.
Sunday, February 19
7:30 am Registration and Morning Coffee
8:25 Organizer's Opening Remarks
8:30 Chairperson's Welcoming Remarks
Raymond Winquist, Vice President, Vertex Pharmaceuticals
8:50 Characterization and Targeting of Human Leukemia Stem Cells
Craig T. Jordan, Ph.D., Professor of Medicine, James P. Wilmot Cancer Center, University of Rochester School of Medicine
Human leukemia stem cells (LSCs) are preferentially resistant to many forms of conventional therapy and represent a significant challenge to the development of improved regimens for leukemia patients. We have demonstrated that certain classes of compounds are able to direct target LSCs, while also sparing normal hematopoietic stem and progenitor cells. Agents capable of eradicating LSCs function via a multiparameter mechanism in which pathways related to oxidative balance, stress response, and survival are simultaneously modulated. Data will be presented describing such pathways and strategies to create strategies for therapeutic targeting of human LSCs.
9:20 Translating the Cancer Stem Cell Hypothesis from the Lab to the Clinic
William Matsui, M.D., Associate Professor of Oncology, Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
Cancer stem cell targeting approaches are rapidly emerging, but it is unclear how to best evaluate their efficacy in the clinical setting. Translational considerations, including clinical trial design, outcome measures, and biomarker strategies will be discussed.
9:50 Networking Coffee Break
10:30 Will Telomerase Inhibitors Target Cancer Stem Cells?
Jerry W. Shay, Ph.D., Professor, Department of Cell Biology, University of Texas Southwestern Medical Center
Do cancer cells with stem cell properties have long or short telomeres? Are cancer cells with stem cell properties mostly quiescent? These critical questions will be discussed in the context of ongoing telomerase inhibitor clinical trials.
11:00 Unraveling Leukemia Stem Cell Survival Mechanisms
Kristen M. Smith, Ph.D., Project Leader, Jamieson Lab, Moores Cancer Center, University of California San Diego
Leukemia stem cells display splice isoform switching which enable them to co-opt stem cell properties and evade therapies targeting proliferating cells. Anti-leukemia stem cell therapy together with splice isoform biomarkers may provide for cancer stem cell detection and eradication of refractory malignancies.
11:30 SMO Independent Blockers of HH Signaling
Daniel Vitt, Ph.D., CSO, 4SC AG
Since resistance formation potentially limits therapeutic use of SMO antagonists this presentation will introduce a novel class of small molecules which selectively block hedgehog signaling in a SMO receptor independent way with a special focus on cancer stem cell phenotypes.
12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:25 Chairperson's Remarks
Raymond Winquist, Vice President, Vertex Pharmaceuticals
1:30 Divergent Roles of the Coactivator Proteins CBP and p300 in Stem Cells and Cancer Stem Cells
Mike Kahn, Ph.D., Professor of Biochemistry and Molecular Biology; Provost's Professor of Medicine and Pharmacy, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California
We have demonstrated that a CBP/catenin-mediated transcription cassette is critical for the maintenance of CSCs. The specific CBP/catenin antagonist, PRI-724, is currently in Phase I. It has proven extremely safe and effective as judged by reduction of the biomarker survivin.
2:00 Development of Novel Small Molecule Anti-Cancer Agents that Selectively Target Cancer Stem Cells
Jonathan Pachter, Ph.D., Vice President & Head, Research, Verastem, Inc.
Verastem is a Biotech company focused on development of drugs that selectively target cancer stem cells. Based on our observation that the epithelial-mesenchymal transition (EMT) induces a cancer stem cell phenotype, we have used EMT induction to establish unique CSC assays providing a robust platform for high-throughput screening. We are currently developing selective lead agents which have been optimized following the screening of more than 300,000 compounds. Cellular assays used to screen for CSC-selective agents will be described, and data will be presented showing in vitro and in vivo effects of representative compounds. Biomarkers useful for clinical proof-of-concept will also be presented.
2:30 EMT and the Cancer Stem Cell State: A Lens for Treatment Combinations
John D. Haley, Ph.D., Senior Research Director, OSI Pharmaceuticals LLC, a wholly owned subsidiary of Astellas US
Tumor tissues are comprised of heterogeneous collections of cell types and cell states utilizing distinct signaling networks. The role of EMT and cancer stem cells in promoting cellular heterogeneity and drug resistance, guiding the combination of anti-cancer agents is discussed.
3:00 Networking Refreshment Break with Poster Viewing
3:30 Overcoming Cancer Stem Cell Treatment Resistance
Maximilian Diehn, M.D., Ph.D., Assistant Professor, Department of Radiation Oncology, Cancer Institute; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine
Cancer stem cells (CSCs) are often relatively resistant to standard treatments, including chemotherapy and radiotherapy. Multiple CSC resistance mechanisms have been identified and may be tumor type specific. Overcoming CSC resistance is a promising approach for improving clinical outcomes.
4:00 A New Model Recapitulating Colon Cancer Differentiation Provides Evidence for Intestinal Stem Cell Origin of Cancer Stem Cells
Jennie Mather, Senior Vice President, Stem Cell Technologies, Macrogenics, Inc.
Cancer stem like (CSLC) cell lines were selected in defined medium that formed tumors and metastasized. While some lines were negative for CD44, CD133 and ALCAM; all expressed the ISC associated markers, ALDH1, ASCL2, LGR5, SOX9 and bound anti-SSEA1 antibody.
4:30 Pre-Clinical Development of OMP-18R5: A Novel Wnt Pathway Antagonist with Anti-CSC Activity
Tim Hoey, Senior Vice President, Cancer Biology, Oncomed
Cancer stem cells (or tumor initiating cells) mediate tumor progression, metastasis, and recurrence after therapy. The Wnt/β-catenin pathway is known to play a critical role in stem cell self-renewal and is de-regulated in several major cancer types. We have developed a novel Wnt pathway antagonist antibody, OMP-18R5, which blocks Wnt binding to FZD receptors and canonical signalling to β-catenin. In xenograft studies with patient-derived tumors, OMP-18R5 inhibited the growth of a broad range of tumors and reduced cancer stem cell frequency.
5:00 Close of Day