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
10:45 Targeted NGS Applications for Detection of Somatic Mutations
Oleg 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.
11:15 Accelerating Preclinical Drug Development by in vivo and ex vivo Imaging in Cancer Models: Optimizing Discovery to Delivery
Werner 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.
11:45 FEATURED PRESENTATION: The Critical Role of Extracellular Matrix and Microenvironment in Metastasis and Dormancy
Mina 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.
12:00 pm Luncheon Presentation: Targeting Epigenetics Using Human Cell Model Systems and Novel In Vitro Assays
Elizabeth R. Quinn, Ph.D., Director, LeadHunter Discovery Services, DiscoveRx Corporation
DiscoveRx’s in vitro assays and human model systems enable inhibitor characterization based on target profiles and effects on complex biological systems. Bromodomain inhibitor potency and selectivity was evaluated using BROMOscan™ quantitative binding assays and intracellular target engagement assays. Inhibitors were classified based on their phenotypic impact on primary human cell systems using BioMAP®. These assays can guide compound prioritization, indication selection and highlight potential safety issues to improve clinical success.
12:50 pm Chairperson’s Opening Remarks
1:00 FEATURED PRESNTATION: An All-Human Microphysiologic Liver System for Carcinoma Metastasis
Alan 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.
1:30 Ex vivo Tumor Tissue Model for Patient-Specific Drug Screens
Geoffrey 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.
2:00 Phenotypic Profiling of Compound Activity in Cultured Human Tumour Tissues
Leo 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.
2:30 Sponsored Presentations (Opportunities Available)
3:00 Refreshment Break in the Exhibit Hall with Poster Viewing
3:45 Use of Repository and Newly Established Cell Lines to Model Cancer Drug Sensitivity and Resistance
Cyril 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 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 Sponsored Presentations (Opportunities Available)
5:15 A Novel Approach to Overcome Oncogenic Addiction via 3D Model Systems
Hakim Djaballah, Ph.D., Director, HTS Core Facility, Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center
Classical drug discovery approaches for oncology have relied heavily on killing cancer cells; they have worked very well in some cases but not as good as predicted in others with many failures reported the clinic. We have taken an opportunistic approach looking for small molecules which would selectively revert the addictive state of the cancer cell yielding a vulnerable phenotype. I will describe the approach and discuss our findings thus far with the ultimate goal of progression to the clinical.
5:30 PANEL DISCUSSION: Increasing Predictability of in vitro Tumor Models
Panelists: Speakers of the Day
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.