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Novel In Vitro Models of Cancer

Predicting whether a potential new anticancer agent will be effective in patients remains a challenge. Murine models, the traditional preclinical hosts for cancer compound testing, have considerable limitations, and scientists are constantly searching for better technologies for in vitro tumor modeling. In the last several years considerable progress was made in the area of 3D tissue models as well as the development of novel approaches using cancer cell lines. Cambridge Healthtech Institute’s Inaugural Novel in vitro Tumor Models conference is designed to present the latest advances in engineering and applications of novel in vitro/ex vivo tumor models.

Day 1 | Day 2 | Oncology Brochure 

Thursday, May 22

9:30 am Registration

Bridging Session between Four Oncology Tracks**

10:30 Bridging Session Chair
Jonathan Wall, Ph.D., University of Tennessee Graduate School of Medicine

10:35 Targeted NGS Applications for Detection of Somatic Mutations

Oleg IartchoukOleg Iartchouk, Ph.D., Director, Genomics and Next-Generation Sequencing, Novartis Institutes for Biomedical Research

This talk will give an overview of NGS applications used to discover somatic point mutations and short insertion deletions in different types of cancer samples. Potential promise for some of them in clinical settings will be discussed.

11:05 Accelerating Preclinical Drug Development by in vivo and ex vivo Imaging in Cancer Models: Optimizing Discovery to Delivery

Werner ScheuerWerner Scheuer, Research Leader, Pharma Research and Early Development, Discovery Oncology, Roche Diagnostics GmbH

The presentation will discuss the following topics: application of different imaging modalities to monitor the efficacy of compounds on primary tumor growth, metastasis and angiogenesis; simultaneous measurement of Pk and Pd; optimizing application schedules regarding combination therapies; and verification of in vivo imaging data by 3-dimensional multispectral fluorescence histology.

11:35 FEATURED PRESENTATION: The Critical Role of Extracellular Matrix and Microenvironment in Metastasis and Dormancy

Mina BissellMina J. Bissell, Ph.D., Distinguished Scientist, Life Sciences Division, Lawrence Berkeley National Laboratory

I will discuss why and how we developed, and use, 3-dimensional models of normal mammary gland and mammary tumors from both mice and humans to understand breast cancer, and will present recent work, shedding light on why tissue and organ architecture should become also a parameter in cancer research, and how architecture can regulate tissue-specificity as well as the plasticity of tumors.  I will also discuss newer and more complex models we have developed to understand metastasis and dormancy and a screen that has allowed us to discover a new class of ‘oncogenes’ in the EGFR/PI3 Kinase.

ONCOdesign Biotechnology12:05 pm An Integrative Approach to the Evaluation, Selection and Orientation of Novel Cancer Therapeutics

 JonathanewingJonathan Ewing, Business Development, Director, OncoDesign 

The challenge in identifying the preclinical activity of cancer therapeutics and orientating their best clinical use is associating relevant in vivo models of human disease with effective pharmacological evaluation and biomarkers.  Oncodesign’s precision medicine approach to clinical drug candidate selection integrates appropriate in vivo models, extensive pharmacological expertise and pharmaco-imaging tools to provide quantitative, predictive and translational evidence early in drug development.

Human Tissue Models and Patient-Specific Screens

1:25 pm Chairperson’s Opening Remarks
Alan Wells, M.D., Ph.D., Associate Chair, Pathology, University of Pittsburgh Medical Center

1:30 FEATURED PRESNTATION: An All-Human Microphysiologic Liver System for Carcinoma Metastasis

Alan WellsAlan Wells, M.D., Ph.D., Associate Chair, Pathology, University of
Pittsburgh Medical Center

Metastases kill patients, but disseminated cancers are resistant to therapies. The tumor biological events behind this are unknown due to lack of relevant model systems. Further, humans metabolize agents and present toxicities uniquely, hampering drug development. We have developed an all-human microphysiological system of the liver to study both tumor behavior in the common metastatic site, and drug metabolism/efficacy in the main metabolizing organ.

2:00 Ex vivo Tumor Tissue Model for Patient-Specific Drug Screens

Geoffrey BartholomeuszGeoffrey Bartholomeusz, Ph.D., Assistant Professor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

The inability to replicate tumor heterogeneity utilizing in vitro cell culture models have prevented these studies from being successfully translated into clinical practice. Prolonged time, high costs and resource consuming have slowed the development of patient-derived xenograft models. The relevance of an ex vivo tumor tissue in identifying a patient specific single agent of drug cocktail will be discussed.

2:30 Phenotypic Profiling of Compound Activity in Cultured Human Tumour Tissues

Leo PriceLeo Price, Ph.D., Principal Investigator, Toxicology, Leiden Amsterdam Center for Drug Research

To bridge the gap between in vitro and in vivo models for cancer, we developed an ultra-high content screening platform for human tumour tissues. Using 3D tissues cultured from cell lines and patient-derived cancer stem cells, compounds can be profiled in a context that more closely simulates the patient situation. Screening in tissues derived from the same cell lines that will be used in xenograft models is also predicted to improve the concordance of in vitro and preclinical data. This approach is expected to significantly reduce the proportion of compounds that fail in pre-clinical studies.

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


3:40 Chairperson's Remarks
Leo Price, Ph.D., Principal Investigator, Toxicology, Leiden Amsterdam Center for Drug Research

3:45 Use of Repository and Newly Established Cell Lines to Model Cancer Drug Sensitivity and Resistance

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

I will discuss the use of large cell lines collections to identify candidate biomarkers of therapeutic response and of cell lines newly derived from tumors with acquired resistance to provide valuable insights into the mechanisms underlying resistance and discover novel therapeutic modalities.

4:15 An Evolving View of Cancer: Studying the Emergence of Resistance to Targeted Agents Using Colony Growth Kinetics and a 3D Culture System

Arijit ChakravartyArijit Chakravarty, Ph.D., Senior Scientist II, Modeling and Simulation, DMPK, Takeda Pharmaceuticals

The changing picture of the landscape of carcinogenesis and tumor response to therapy frames cancer as a disease of genomic instability and somatic Darwinian evolution. Developing realistic model systems and methodologies to study heterogeneity and evolution in populations of cancer cells would be the first step in leveraging the emerging picture of cancer in Oncology drug development. In this presentation I will discuss the challenges posed by tumor heterogeneity and evolution, and the methods by which a novel 3D soft agar system allows us to study this process. We extract the growth kinetics of individual colonies via high-content analysis, and then couple this with mathematical modeling, to identify novel insights on the emergence of resistance to targeted agents.

4:45 Determination of Target Engagement on Cancer Targets in vitro and in vivo
Michael Dabrowski, Ph.D., CEO & Co-Founder, Pelago Bioscience AB
We have developed a generic method for evaluating drug binding to target proteins in cells and tissues (Martinez Molina et al. Science 2013). The CEllular Thermal Shift Assay (CETSA™) is based on the physical phenomenon of ligand-induced thermal stabilization of target proteins. Using this technique, it is possible to quantify physiological relevant drug-target interactions in cells and tissue completely label free. We have validated drug binding in mammalian cancer cell lines for a set of important clinical targets and show that a range of critical factors that are important for drug development can be identified at the target engagement level, including drug transport and activation, off-target effects, drug resistance as well as drug distribution in animal tissues.
5:15 Selected Poster Presentations 

5:30 PANEL DISCUSSION: Increasing Predictability of in vitro Tumor Models 

Moderator:  Leo Price, Ph.D., Principal Investigator, Toxicology, Leiden Amsterdam Center for Drug Research 

6:15 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.

Suggested Event Package:

May 22-23

Pre-Conference Short Course*

How To Best Utilize Organotypic 3D Cell Cultures Assays In Oncology 

* Separate registration required

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