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Predictive Pre-Clinical Models in Oncology

 

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Download World Pharma Congress Final Brochure or Download Pre-Clinical Models Oncology Brochure 

About This Conference:


The Predictive Pre-Clinical Models in Oncology conference is designed to highlight the cutting edge in vitro and in vivo pre-clinical models that allow to more effectively evaluate novel cancer therapeutics as well as to identify predictive biomarkers in early stages of drug development. Case studies and solutions for increasing the predictability of pre-clinical cancer studies will be presented.


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Patient Derived Cancer Tissue Xenograft Models  


TUESDAY, JUNE 5

7:15 am Registration & Morning Coffee

 

PREDICTIVE BIOMARKER IDENTIFICATION IN PRE-CLINICAL MODELS 

8:15 Chairperson’s Opening Remarks

Nancy K. Pryer, Ph.D., Director, Oncology Pharmacology, Novartis Institutes for Biomedical Research 

 

» 8:25 Keynote Presentation

Pre-Clinical Opportunities for Improving Cancer Patient Care: Value and Challenges of Engineered Cancer Models in Therapeutic and Diagnostic Discovery

Terry A. Van Dyke, Ph.D., Head, Mouse Cancer Genetics Program; Program Director, Cancer Pathways and Mechanisms, National Cancer Institute

Despite the promise of “molecularly targeted therapies,” most cancer drugs entering trials fail, usually due to lack of efficacy in patients. Successful treatments are temporary, and the need for biomarkers to stratify patients and monitor responses are also needed. Hence, the accuracy of existing preclinical approaches must be improved. Currently methodologies to engineer mice, genetically and biologically, better model human cancers. Promising preclinical studies and remaining challenges using these models will be discussed.

9:10 From Cell Lines to Mouse Models: Building Pre-Clinical Oncology Models to Match Targeted Therapies to Cancer Patient Populations

Nancy K. Pryer, Ph.D., Director, Oncology Pharmacology, Novartis Institutes for Biomedical Research

The development of targeted therapies for cancer requires an understanding of the characteristics of responsive cancer patient populations to direct the best therapy to the appropriate patients. To approach this goal, Novartis is assembling a suite of pre-clinical models with molecular genetic annotation, including a collection of human tumor cell lines amenable to compound profiling, which is used to generate patient selection hypotheses. These hypotheses can then be tested in novel primary human tumor xenograft models, which are complemented by genetically engineered mouse models and murine allograft models.

9:40 A Hedgehog-Dependent Barrier to Drug Delivery in Pancreatic Cancer - Translation from Mice to Patients

Kenneth Olive, M.D., Assistant Professor of Medicine and Pathology, Irving Cancer Research Center, Columbia University

Pancreatic cancer develops and abundant stroma that interferes with drug delivery. We found that an inhibitor of the Hedgehog pathway breaks down the stroma in a genetically engineered model of pancreatic cancer and facilitates delivery of chemotherapy. Preliminary data from a clinical trial of this combination support further investigation and Phase II studies are under way.

10:10 Coffee Break

10:40 Beyond Cell Lines: Building Confidence in Predictive Markers Using Ex Vivo Drug Treatment Models with Patient Derived Tumor Specimens

Thomas B. Broudy, Ph.D., CSO, Molecular Response 

Studies of cancer cell lines have formed the basis of preclinical oncology research for decades.  This talk will cover recent use of patient derived tumor banks, 3D drug treatment models, cell-based imaging, and molecular profiling to both discover and build confidence in predictive markers prior to evaluation in the clinic.

Champions Oncology 10:55 Find the Right Patients for the Right Drugs: Translatable Predictability for Oncology Drug Development 

Elizabeth Bruckheimer, Ph.D., Vice President, Scientific Operations, Champions Oncology, Inc. 

93% of oncology drugs that enter clinical trials fail to reach the market. The main reason for this is there is no robust method of predicting how patients will respond to oncology drugs before actually treating patients. Champions TumorGraft models are sourced via a unique process which provides a more realistic and predictive model for translating high value clinical development strategies from the bench to bedside.

11:10 Discovery of Candidate Biomarkers of Anticancer Drug Sensitivity by High-Throughput Cell Line Screening

Cyril H. Benes, Ph.D., Principal Investigator and Director, Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center 

Building on the pioneering efforts of the national cancer institute using human tumor derived cell lines as tractable model for the study of drug sensitivity (the panel of 60 cell lines known as the NCI60) we have assembled a collection of 1,000 cell lines representative of the majority of adult and childhood cancers. We use this cell line collection to define molecular determinant of drug sensitivity in vitro as a first step towards defining biomarkers of drug response in patients. Overall, our studies reveal many novel sensitizing and drug resistance correlates that could lead to the identification of biomarkers useful for the development and application of cancer therapeutics.

11:40 Assessing Therapeutic Responses in Genetically Engineered Mouse Models of Cancer

Mallika Singh, Ph.D., Investigator III, Novartis Vaccines and Diagnostics, Inc. 

The high failure rate of late-stage human clinical trials, particularly in oncology, predicates the need for improved translation of pre-clinical data from mouse tumor models into clinical predictions.  Genetically engineered mouse models (GEMMs) may better fulfill this need because they mimic spontaneous and autochthonous disease progression.  This talk will review the successful pre-clinical application of such GEMMs, including the potential for discovery of predictive biomarkers and for mechanistic insights into clinical outcomes and drug resistance in human cancers.

Vivo Biosciences 12:10 pm New 3D Micro-tumor Assay Systems for Preclinical and Predictive Oncology Programs: Replicating Human Tumor Biology In VitroRaj Singh, Ph.D., President & CEO, VIVO BIOSCIENCES, INC.At present monolayer (2D) cell-based assays and animal xenograft models are commonly used for basic and preclinical drug discovery programs.  Physiologic importance of 3D or multicellular cultures (colony, spheroid) are also recognized, however a robust in vitro bioassay platform for human tumors is not yet available.  VBI has developed a patented 3D HuBiogel cultivation technology which allows production of hundreds of tumor-constructs exhibiting in vivo-like morphology, organization and functions. A series of human micro-tumor assay systems emulating monotypic, heterotypic and hypoxic environments are established using automated co-culture protocols with NCI-60 cell lines and patient-derived tumor cells/fragments.  Moreover, 3D tumors maintain long-term viability and actively respond to differing gradients of specific growth factors and cancer drugs.  Real-time imaging, functional and genomic profiling are performed with high throughput to monitor tumor growth, invasion, hypoxia and angiogenesis (96-384 assay formats).  Validation and case studies include in-vivo like tumor biology endpoints, identifying new/good drug candidates, why a lead cancer drug failed and precise drug sensitivity analysis with patient tumors.  In brief, new micro-tumor bioassays offer an advanced preclinical and predictive platform for making better go/no go decisions prior to expensive clinical studies.  

12:25 Luncheon Presentation 

Applications of Global Metabolomics in Drug DiscoveryMike Milburn, Ph.D., CSO, Metabolon, Inc. 
The small molecule metabolome is fast becoming a key constituent to translational research, and an incisive companion for R&D and biomarker discovery. Metabolon offers a comprehensive platform that provides a global metabolomic analyses of biological systems incorporating advanced metabolomic software with multiple separation platforms. This integrated platform provides increased overall coverage of small molecules and allows robust, fully industrialized access to metabolomics discoveries. A selection of case studies will be presented.

1:10 Session Break

 

NOVEL ANIMAL MODELS 

1:30 Chairperson’s RemarksCedo Bagi, M.D., Ph.D., Senior Research Fellow, Worldwide Comparative Medicine, Global Science & Technology, Pfizer Global R&D 

1:40 Future Advances in Oncology Drug Development: Characterization Patient-Derived Explants in Comparison to Standard Human Tumor Cell Line-Derived Xenografts

Ching Ching Leow, Ph.D., Senior Scientist, MedImmune, an Astra Zeneca company 

Patient-derived explant models (PTX) show a higher genetic and pathological heterogeneity and may have greater clinical relevance in cancer drug development and personalized oncology treatments than cell line derived xenograft models. Consequently, the use of panels of PTX models has the potential to provide additional confidence in, and the refinement of, patient stratification hypotheses for novel therapies or combination approaches. Talk will take comprehensive review of internal studies and those cited within the literature.

2:10 Exploring of Non-Germline Genetically Engineered Mouse Cancer Models for Translational Discovery and Pre-Clinical Drug Development

Serguei Kozlov, Ph.D., Principal Scientist, Center for Advanced Pre-Clinical Research, SAIC-Frederick, Inc. 

Non-germline genetically engineered mouse (NG-GEM) models recently introduced into translational and pre-clinical oncology fields provide a robust option for efficacy drug evaluation that is more predictive of clinical outcomes compared to traditional xenograft models. We launched a broad-scope initiative to develop and optimize different types of NG-GEMs for therapeutically most challenging malignancies, including brain, serous epithelium ovarian and lung cancer, as well as melanoma.

2:40 The JAX Patient Derived Xenograft (PDX) Cancer Consortium: Changing the Course of Clinical Advancement

Neal Goodwin, Ph.D., Director, Research and Development, In Vivo Pharmacology Services, The Jackson Laboratory 

A collaborative effort between JAX, the UC-Davis Comprehensive Cancer Center, and other research centers has been established for advancing cancer therapeutic development. Solid and liquid tumor specimens from consenting patients are being transplanted into the JAX-NSG mouse which has been engineered to ideally propagate human tissue. Over 400 patient specimens have been xenografted into NSG mice and over 100 PDX tumor models have been advanced for use in research including co-clinical predictive tumor response studies.

3:10 Is the Use of Orthotopic Oncology Models a Necessity or a Luxury?

Cedo Bagi, M.D., Ph.D., Senior Research Fellow, Worldwide Comparative Medicine, Global Science & Technology, Pfizer Global R&D 

The overall success rate for oncology products in clinical development remains frustratingly low and results from studies in subcutaneous xenograft models fail to predict clinical outcomes as they lack some of the key elements of human cancers.  The role of specific organ stroma and vascularization are major determinants of tumor cell engraftment, survival, local growth and dissemination.  Adequate use of heterotopic tumor models allow for a more realistic assessment of drug efficacy in patients.

3:40 Refreshment Break in the Exhibit Hall with Poster Viewing

4:40 Interactive Discussion Groups

Concurrent problem-solving discussions on specific topics, to provide a forum for exchanging ideas, voicing opinions and meeting potential collaborators. Discussions will be led by a moderator/s, limited to 15 participants per table, and open to all attendees and exhibitors.

Translation from Mice to PatientsKenneth Olive, M.D., Assistant Professor of Medicine and Pathology, Irving Cancer Research Center, Columbia 

Industry-Academia collaboration in The Area of Cancer ModelsMila McCurrach, Project Manager, NFPC, Neurofibromatosis Pre-Clinical Consortium, Children’s Tumor Foundation 

Cell Lines: Strengths and LimitationsCyril H. Benes, Ph.D., Principal Investigator and Director, Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center 

Genetically Engineered Mouse Models: Strengths and LimitationsMallika Singh, Ph.D., Investigator III, Novartis Vaccines and Diagnostics, Inc.
Patient Derived Xenograft ModelsNeal Goodwin, Ph.D., Director, Research and Development, In Vivo Pharmacology Services, The Jackson Laboratory
 

Biomarker Discovery in Pharma through MetabolomicsMike Milburn, Ph.D., CSO, Metabolon, Inc. 

5:40 Welcome Reception in the Exhibit Hall with Poster Viewing

6:45 End of Day



Day 1 | Day 2 
Download World Pharma Congress Final Brochure or Download Pre-Clinical Models Oncology Brochure