2013 Archived Content
Predictive Pre-Clinical Models in Oncology
Delivering Reproducible and Predictive Results
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Can pre-clinical models predict the results of phase 3 clinical trials? A positive answer to this question would require an implementation of novel strategies of pre-clinical cancer research. Selection of appropriate animal models based on similarity to human biology carries considerable potential to ensure a higher predictability of pre-clinical trials. Innovative in vitro models are equally important for minimizing the odds of pre-clinical errors. Cambridge Healthtech Institute's Inaugural Predictive Pre-Clinical Models in Oncology is designed to highlight the cutting edge in vitro and in vivo pre-clinical models that allow researchers 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.
Wednesday, February 13
7:00 am Registration and Morning Coffee
8:00 – 9:40 am Plenary Keynote Presentation - Personalized Oncology – Fulfilling the Promise for Today's Patients
In honor of the 20th anniversary of the Molecular Medicine Tri-Conference, CHI and Cancer Commons will present a plenary panel on Personalized Oncology. Innovations such as NGS and The Cancer Genome Atlas have revealed that cancer comprises hundreds of distinct molecular diseases. Early clinical successes with targeted therapies suggest that cancer might one day be managed as a chronic disease using an evolving cocktail of drugs.Representing all five conference channels, Diagnostics, Therapeutics, Clinical, Informatics, and Cancer, a panel of experts will lead a highly interactive exploration of what it will take to realize this vision in the near future.
9:40 Refreshment Break in the Exhibit Hall with Poster Viewing
11:00 Chairperson’s Opening RemarksFredika Robertson, Ph.D., Professor, Experimental Therapeutics, The University of Texas MD Anderson Cancer Center
11:10 KEYNOTE PRESENTATION: Development of Pre-Clinical Strategies that Accurately Guide Clinical Cancer Research: Progress, Challenges, &Perspective
Terry A. Van Dyke, Ph.D., Director, Center for Advanced Preclinical Research (CAPR); Head, Cancer Pathways and Mechanisms Section, Center for Cancer Research, National Cancer Institute
11:40 Maximizing Clinical Efficacy Of The Angiopoietin-2 Targeting Agent CVX-060 Based On Preclinical Predictive Biomarkers And Human Tumor Profiling.
Gallen Triana-Baltzer, Ph.D., Senior Scientist, Oncology, CovX Research, Pfizer WRD
In this era of precision medicine there is a growing emphasis on identifying predictive biomarkers to deliver investigational compounds to the appropriate patients. This is particularly true for anti-angiogenic agents which do not show benefit in all patients and for which predictive markers have been especially elusive. CVX-060 is an angiopoietin-2 (Ang2) targeting therapeutic in phase 2 clinical trials. Here we present an extensive preclinical effort to identify a predictive biomarker signature to identify tumors most likely to respond to CVX-060 therapy. Using xenograft models we identify a protein signature of Ang1, EGF/R, and Emmprin that was used to develop a predictive model. Finally human tumor samples were profiled for Ang1 and 2 levels to identify indications with promising target levels for CVX-060 treatment.
12:10 pm Models of Anaplastic Lymphoma Kinase Activation in Breast Cancer
Fredika Robertson, Ph.D., Professor, Experimental Therapeutics, The University of Texas MD Anderson Cancer CenterUsing patient derived tumors and tumor cells, we developed novel models that recapitulate human breast cancer and identified activation of ALK signaling pathways that are linked to Akt-mTor. Genomic and proteomic analysis revealed small molecule ALK inhibitors to be effective in inducing apoptosis, and blocking phospho-Akt-mTor signaling. These studies directly led to screening of a breast cancer patient population who would otherwise be excluded from clinical trials with ALK inhibitors.
12:40 Luncheon Presentation I: Genetically Engineered Miniature Swine Models of Cancer: Bridging the Pre-Clinical Gap from Rodents to HumansJohn Swart, Ph.D., President, Exemplar GeneticsThe development and characterization status of the first two genetically engineered miniature swine models of cancer, a model that should have significant advantages over the currently available rodent models for preclinical predictive efficacy, will be presented during this session.
1:10 Luncheon Presentation II (Sponsorship Opportunity Available) or Lunch on Your Own
1:45 20th Anniversary Cake in the Exhibit Hall with Poster Viewing
2:15 Chairperson’s RemarksRoss Cagan, Ph.D., Professor, Developmental & Regenerative Biology, Mount Sinai School of Medicine
2:20 Is the Use of Orthotopic Oncology Models a Necessity or Luxury?
Pasquale Cirone, Ph.D., Postdoctoral Fellow, Worldwide Comparative Medicine, Global Science & Technology, Pfizer Global R&DThe overall success rate for oncology products in clinical development remains frustratingly poor, in large part because studies utilizing subcutaneous xenograft models cannot predict clinical outcomes as they lack several key elements of human cancers. Through orthotopic animal models, we’ve explored the role of specific organ stroma and vascularization as major determinants of tumor cell engraftment, survival, local growth and dissemination. Adequate use of heterotopic tumor models allowed for more representative assessments of drug efficacy in patients. Still, these models have their limits with regards to predictive value – suggesting a greater necessity for even more complex (or less luxurious) animal models.
2:50 Non-Germline Genetic Mouse Model Strategies for Retooling of Next- Generation Pre-Clinical Murine GEMMs
Serguei Kozlov, Ph.D., Principal Scientist, Center for Advanced Pre-Clinical Research, SAIC-Frederick, Inc.
CAPR employs orthotopic allografting and embryonic/induced pluripotent stem cell technologies to expedite resource conscious building of cohorts for pre-clinical experimentation using“non-germline” models.
3:20 Complex Models & Polypharmacology: A Fly Approach to Therapeutics
Ross Cagan, Ph.D., Professor, Developmental & Regenerative Biology, Mount Sinai School of Medicine
Cancer presents a challenge due to its genomic and tissue complexity. I will discuss our use of Drosophila cancer models that embrace this complexity to develop novel candidate therapeutics.
3:50 The JAX Patient Derived Xenograft (PDX) Cancer Consortium: Changing the Course of Clinical Advancement
Neal Goodwin, Ph.D., Dir., R&D, 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.
4:20 Networking Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunities Available)
5:20 Breakout Discussions in the Exhibit Hall
Genetically Engineered Mouse Models: Strengths and LimitationsModerator: Serguei Kozlov, Ph.D., Principal Scientist, Center for Advanced Pre-Clinical Research, SAIC-Frederick, Inc.- What are the current unmet needs specific for preclinical phase of drug development and which of these needs may be efficiently addressed in genetically engineered murine models?
- What features of GEMMs – either already existing in current models or yet to be engineered – are the most appealing as adding value to preclinical drug development?
- What feature(s) still hinder the broader application of GEMMs in preclinical investigations and how such limits may be addressed?
- Apart from direct efficacy evaluation, what other dimensions/facets of preclinical GEMM applications are, or may become, particularly valuable from the drug development prospective (systems profiling, biomarkers for patient stratification and/or disease severity, molecular signatures of drug response vs. resistance, novel clinically meaningful endpoints, novel drug targets, etc.)?
Industry-Academia collaboration in The Area of Cancer ModelsModerator: Mila McCurrach, Project Manager, NFPC, Neurofibromatosis Pre-Clinical Consortium, Children’s Tumor Foundation, Research Manager, Lustgarten Foundation- Speeding up the MTA process
- Validation of "appropriate" model systems
- Establishing Standard Operating Procedures
New High-Throughput Human MicroTumor Screening PlatformModerator: Raj Singh, Ph.D., President & CEO, Vivo Biosciences, Inc.- Robust 3D tumor screens established with NCI-60 and PDX cell lines
- Validate drug targets under fully-human tumor microenvironment
- Better prediction of anti-tumor efficacy to accelerate preclinical trials
6:20 Close of Day
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