Cambridge Healthtech Institute’s Tumor Models to Guide Targeted Cancer Therapy and Drug Development conference aims to bring together cancer researchers and clinicians working on development of molecularly targeted cancer therapies, and to initiate a knowledge exchange around preclinical models and their optimization. Highly characterized patient-derived tumor tissue xenograft models that allow us to more effectively evaluate novel targeted therapeutics as well as to identify predictive biomarkers in early stages of drug development will be discussed. Case studies and solutions for increasing the reproducibility and predictability of preclinical cancer studies will be presented.
Day 1 | Day 2 | Oncology Brochure
Wednesday, May 21
7:00 am Registration and Morning Coffee
8:00 Chairperson’s Opening RemarksTerry A. Van Dyke, Ph.D., Head, Mouse Cancer Genetics Program; Program Director, Cancer Pathways and Mechanisms, National Cancer Institute
8:05 FEATURED PRESENTATION: Making Decisions with Cell Line and Patient-Derived Xenograft Models in Drug Discovery and Development
Anderson Clark, Ph.D., Director, In vivo Pharmacology, Oncology, EMD Serono Research & Development Institute
The focus of this presentation will be around the ways in which we place different types of in vivo cancer models within the contexts of drug discovery and development at EMD Serono. Cell line xenograft models will be considered, but the emphasis will be on the use of patient-derived tumor models -- when and how do we use them, how do we interpret the data and how do we translate those data for clinical decision-making.
8:35 FEATURED PRESENTATION: The Application of Primary Tumorgraft Models of B-Raf Mutated Melanoma and Colorectal Cancer to Support the Clinical Development of a CEP-32496, a Potent and Selective Dual Orally-Active Inhibitor of B-Raf and EGFR
Bruce Ruggeri, Ph.D., Senior Director, Oncology Discovery Research, Global R&D, Teva Pharmaceuticals, Inc
BRaf inhibitors are a clinically-validated targeted cancer therapy. Primary human tumorgraft models of melanoma and colorectal cancer with BRaf mutations were utilized to characterize and differentiate CEP-32496, a novel and selective dual BRaf-EGFR inhibitor on the basis of its efficacy and tolerability profiles, from FDA-approved competitor BRaf inhibitors and define a new therapeutic opportunity for the treatment of B-Raf mutated colorectal cancers.
9:05 Tumorgraft Avatar Platform for Clinical Advancement
Neal Goodwin, Ph.D., Vice President, Corporate Research Development, Champions Oncology, Inc.
A patient-derived xenograft (TumorGraft) platform has been established where patient tumors are engrafted to form mouse-avatar TumorGraft models for translational and clinical studies. Therapeutic treatment responses in these mouse avatars are being used prospectively to guide patient treatment and the avatar-directed treatment outcomes correlated with patient treatment outcomes.
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:15 Chairperson’s Opening RemarksNeal Goodwin, Ph.D., Vice President, Corporate Research Development, Champions Oncology, Inc.
10:20 FEATURED PRESNETATION: Preclinical Evaluation in Engineered Cancer Models: A Path to Accelerated Clinical Development?
Terry A. Van Dyke, Ph.D., Head, Mouse Cancer Genetics Program; Program Director, Cancer Pathways and Mechanisms, National Cancer Institute
Progress in the emerging area of human-predictive preclinical animal model platforms will be overviewed. Our work in this arena is carried out at the NCI Center for Advanced Preclinical Research (NCI-CAPR), a novel initiative developed by the Center for Cancer Research (CCR, NCI). CAPR achieves its mission to develop efficient and predictive preclinical strategies through extensive internal and collaborative partnerships. Recent and ongoing studies in one or more of the following areas will be discussed: pancreatic cancer, glioblastoma, lung adenocarcinoma, melanoma and/or serous ovarian cancer.
10:50 Modeling Tumor Cell Dormancy in the Mouse
Jeffrey E. Green, M.D., Chief, Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute
Tumor recurrence may occur from the reactivation of dormant tumor cells into clinically manifest metastatic disease, which is a major cause of patient morbidity and mortality. The use of in vitro and in vivo models to decipher mechanisms of tumor cell dormancy and their use for preclinical testing will be presented. Translating these findings may greatly improve patient outcome.
11:20 Tumor Models Facing New Challenges
Thomas Metcalfe, Managing Director, Oncotest GmbH
Advances in our understanding of the complexity of cancer -including tumor heterogeneity, the role of the tumor micro-environment and the ability of tumors to evolve under therapy- present increasing challenges to the models used to support the discovery and preclinical development of anti-tumor therapies. Oncotest, as pioneers in the field of Patient Derived Xenografts, are continuously developing and adapting their modelling system to help clients better address these challenges.
11:50 The Co-Clinical Trial Paradigm: Improving Predictive Value of Preclinical Studies
Andrew L. Kung, M.D., Ph.D., Director, Pediatric Hematology, Oncology and Stem Cell Transplantation, New York-Presbyterian Morgan Stanley Children’s Hospital, Columbia University Medical Center
Conventional mouse studies are poor predictors of efficacy in human clinical trials. The predictive value of preclinical studies may be improved by utilizing newer models that recapitulate the complexity of human disease, along with response criteria that are better aligned with clinical measures of success. The use of genetically engineered mouse models, patient-derived xenografts, and molecular imaging will be reviewed in the context of the co-clinical trial paradigm.
12:20 Efficacy Axl-Inhibitor on PDX Model of Bladder Cancer (PDX-BL0293)
Cedo Bagi, M.D., Ph.D., Senior Research Fellow, Worldwide Comparative Medicine, Global Science & Technology, Pfizer Global R&D
Axl is a receptor tyrosine kinase that is expressed in various human cancers and is associated with invasiveness and metastasis. Pfizer’s Axl-inhibitor compound was tested in a patient-derived xenograft (PDX) model of bladder cancer against standard of care.
12:50 Luncheon Presentation I: Using of Patient Derived Engraft Models to Support Preclinical Trials of Oncology Therapeutics
Thomas B. Broudy, Ph.D., CSO, Molecular Response LLC
The depth and breadth of the Molecular Response tumor bank (144k specimens, 76 clinical diagnoses) enables broad-based PDX studies in patient populations meeting specific inclusion/exclusion criteria, such as: mutational status, failed prior therapy or metastatic lesions. By approximating clinical trials in the preclinical setting, we help our partners to establish more confident clinical development strategies--responsive patient populations, effective combination agents, predictive diagnostic tests, and strategies to delay resistance.
1:20 Luncheon Presentation II (Sponsorship Opportunity Available)
1:50 Session Break
2:00 Chairperson’s RemarksJonathan Wall, Ph.D., Professor of Medicine, Human Immunology and Cancer Program; Director, Amyloid and Preclinical Molecular Imaging Laboratory, University of Tennessee Graduate School of Medicine
2:05 Translatability of Preclinical Modeling: Case Study of Development of a Targeted Therapeutic with an Imaging Companion Diagnostic
Ingrid Joseph, D.V.M., Ph.D., Senior. Director, Pharmacology, Agensys, an affiliate of Astellas Pharma, Inc.
Traditional xenograft models utilize immortalized cancer cells grown on plastic that exhibit a genetic drift. Therefore, they do not represent the total genetic/epigenetic heterogeneity of the original cancers. Despite demonstrating efficacy in these models, a majority of cancer therapeutics fail in the clinic. Patient derived tumors grown as xenografts (PDXs) appear to maintain the histopathology/molecular characteristic of the original tumor. A case study utilizing PDX models better suited for targeted therapy will be discussed.
2:35 Molecular Imaging for Patient Selection and Predicting Treatment Response
Paul Acton, Scientific Director and Janssen Fellow, Global Head, Molecular Imaging, Johnson & Johnson
Personalized medicine would provide the key diagnostics required to deliver more effective targeted therapies, avoiding unnecessary or ineffective treatments, and reducing side effects. This presentation will outline several approaches to developing predictive imaging biomarkers, including imaging of labeled drugs, and a novel approach to tagging biologics which allows each drug to become its own companion diagnostic.
3:05 Heparin-Reactive Peptides Preferentially Co-Localize in vivo with Extracellular Melanin – A Novel Biomarker in Metastatic Melanoma Tumors
Jonathan Wall, Ph.D., Professor of Medicine, Human Immunology and Cancer Program; Director, Amyloid and Preclinical Molecular Imaging Laboratory, University of Tennessee Graduate School of Medicine
Melanoma is the most deadly form of skin cancer with >70,000 individuals diagnosed in 2011 in the USA. During a routine histochemical screen of biotinylated heparin-reactive peptides with a tumor tissue array, we identified certain reagents that preferentially bound melanocytic melanoma tumors. We have now demonstrated peptide reactivity, by using SPECT/CT imaging, co-localization of the peptides with B16F10 murine “metastatic” melanoma tumors within the mouse lung.
3:35 Preclinical and Clinical Applications of Patient Derived Xenograft (PDX) Models;
Yan Yang, Director, Lab Operations in vivo Services, The Jackson Laboratory
The Jackson Laboratory has established a unique collaboration with over 20 clinical centers to advance cancer treatment. Patient tumors transplanted into the NSG mouse are being screened with SOC and experimental therapeutics for preclinical research or the refinement of patient treatment regimens.
4:05 Modeling Human Cancer: A Multifaceted Approach to Pre-Clinical Development
Maria L. Mancini, Ph.D., Principal Investigator, Biomodels, LLC
There are a number of key points to consider when designing therapeutics for the treatment of human cancers. Tumor heterogeneity, stromal contribution, immune response, and treatment resistant sub-populations are all potential confounds that complicate the assessment of novel therapeutic strategies in a pre-clinical setting. Only recently have efforts been directed at treating resistant cell populations (often termed cancer stem cells).
4:20 Refreshment Break in the Exhibit Hall with Poster Viewing
5:00 Plenary Keynote Presentation:
Catalyzing Translational Innovation
Christopher P. Austin, M.D., Director, National Center for Advancing, Translational Sciences, National Institutes of Health
6:00 Welcome Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
Day 1 | Day 2 | Oncology Brochure
Five Programs Dedicated to Preclinical Models in Oncology at World Pharma Congress 2014
Despite tremendous progress in our understanding of cancer biology, most novelanticancer therapies fail in Phase III clinical trials. Can we break this paradigm with more predictive preclinical studies? Join pharmaceutical, biotech and academic stakeholders May 21-23 in Boston, for interactive sessions, panel discussions and short courses all geared toward providing opportunities for active networking and collaborating, while gaining strategic insights into solutions for increasing the reproducibility and predictability of preclinical cancer studies.