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Cancer Profiling and Pathways: Next Sequence in the War against Cancer

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Wednesday, February 3

7:00 AM Registration and Morning Coffee

Plenary Keynote Session

8:10 When Drug Research is Personal

John F. Crowley, Founder, Novazyme Pharmaceuticals, Inc.

Mr. Crowley’s emotion-packed presentation will focus on his personal struggle to find a cure for Pompe disease, a rare and fatal illness that is caused by a defective or missing enzyme. Pompe disease affects fewer than 10,000 people world-wide, including Mr. Crowley’s two small children. Mr. Crowley, a Harvard educated businessman, created and built a pharmaceutical company devoted expressly to finding a cure for the disease. He will detail his journey through the labyrinth of scientific and business fronts, which lead up to a first-round clinical trial.

8:55 Technology, Aging, and the Brain

Gary W. Small, M.D., Parlow-Solomon Professor on Aging, Professor of Psychiatry & Biobehavioral Sciences, Director, UCLA Center on Aging, Director, Memory & Aging Research Center, Director, Geriatric Psychiatry Division, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA

New neuroimaging and other technologies are teaching us about how the brain ages and what we can do about it. Although memory declines as we age, medical and nonpharmacological strategies may protect brain health and improve memory performance. At the same time, innovation in digital technology is not only changing the way we live and communicate, it appears to be altering how our brains function. As a consequence of this high-tech stimulation, we are witnessing the beginning of a new form of the generation gap – a brain gap dividing younger digital natives, immersed in the technology early in life, from older digital immigrants, who adapt to the new technology more reluctantly. This lecture will describe this current pivotal point in brain evolution and how we can harness the new technology and lifestyle choices to improve memory and brain function so we can live better and longer. 

9:40 Grand Opening Refreshment Break in the Exhibit Hall

 

KEYNOTE PRESENTATIONS

11:00 Chairperson’s Remarks

Michael Liebman, Ph.D., Managing Director, Strategic Medicine, Inc.

11:10 Personalizing Medicine: It’s a System-Based Challenge

Franklyn G. Prendergast, M.D., Ph.D., Professor, Pharmacology, Biochemistry & Molecular Biology, Director, Center for Personalized Medicine, Mayo Clinic

 

 

 

 

11:40 Genomic Strategies for Personalized Cancer Treatment

Joseph R. Nevins, Ph.D., Barbara Levine Professor, Breast Cancer Genomics, Center for Applied Genomics & Technology, Duke University

Perhaps the major challenge in developing more effective therapeutic strategies for the treatment of most major cancers is confronting the heterogeneity of the disease, recognizing that most cancers are not one disease but multiple disorders with distinct underlying mechanisms. We have made use of expression profiling to develop signatures of oncogenic pathway deregulation that can then be used to profile the state of these pathways within populations of tumors. In addition, the pathway signatures also link the patterns of pathway activation with therapeutics since we have shown that predicting the activation of a pathway also predicts sensitivity to drugs that target the pathway. We have extended this concept to develop more refined signatures that can dissect the complexities of many of the known signaling pathways, providing a more precise capacity to probe the activity or deregulation of the pathway and linking to a broader array of therapeutics. We suggest that this approach can provide a framework for an overall strategy towards the development of personalized treatment options for the individual patient, including strategies for personalized combination therapy.

12:10 PM Panel: Impact of Personalized Medicine on Oncology Drugs and Treatment

Additional Panelist: Mike Boswood, President, CEO, Thomson Reuters

  • How could information about differences of individuals become a way to improve drug discovery rather than reduce ROI?
  • How can you change it to bring in new knowledge?
  • How do you change perception of culture?
  • Is it purely technology that is needed to solve the problem?

12:40 Luncheon Presentation I
Digital, Multiplexed Measurements of up to 550 mRNAs in Clinically Relevant Sample Types Using the nCounter™ Analysis System

Gary Geiss, Ph.D., Principal Scientist, NanoString Technologies, Inc.

The nCounter Gene Expression System utilizes color-coded molecular barcodes to digitally count nucleic acid molecules in solution. The system is capable of measuring over 550 different nucleic acid species in a single reaction without reverse transcription or PCR amplification. The lack of enzymes allows for direct measurements of mRNA from a variety of input materials including degraded RNA (e.g. from formalin-fixed paraffin-embedded (FFPE) tissues) or crude cell lysates (e.g. from tissue or blood). Due to its ease of use, high multiplexing capabilities, and digital readout the system is ideal for validation studies of gene sets derived from discovery platforms such as next generation sequencing or microarrays. New applications of the nCounter System such as miRNA profiling and DNA copy number measurement are currently under development.We will present an overview of the technology and examples of how it has been used to measure multi-gene expression cancer signatures and mRNA fusion-transcripts. 

Sponsored by

1:10-1:40 Luncheon Presentation
A Novel Genome-Wide Screening Application Using Pooled Viral miRNA-adapted shRNA (shRNAmir) Libraries
Katie Jansen Spayd, Ph.D., Research Scientist, Thermo Fisher Scientific
Pooled shRNA libraries are powerful genetic discovery tools that allow for high-throughput screening of the entire genome in a cost-effective and less labor-intensive manner. Unlike arrayed shRNA library approaches requiring many multi-well plates, screens using lentiviral shRNA pools can be performed in a single tissue culture plate. Clonal populations of cells expressing an individual shRNA become enriched or depleted in this mixed population in response to a selective pressure. Genes required for cell enrichment or cell depletion can then be deconvoluted by next-generation sequencing or microarrays hybridized with barcode sequences corresponding to each shRNA in the pool. Here, we present a novel pooled shRNA screening approach for identifying regulators of endogenous gene expression. Epithelial cell adhesion molecule (EpCAM), a cell surface receptor that is highly expressed in a variety of tumorigenic cells, promotes cell proliferation and tumor formation via transcriptional activation of mitogenic genes. Thus, EpCAM represents a target for the development of new cancer therapeutics. We performed a whole-genome pooled shRNA screen to identify novel regulators of EpCAM expression. OVCAR8 cells were transduced with the Thermo Fisher Scientific Decode™ RNAi Viral shRNAmir Pools. Following puromycin selection, we used magnetic-activated cell sorting (MACS) to separate cells on the basis of EpCAM protein expression. Genomic DNA was isolated from EpCAM+ and EpCAM- cells and the shRNAs enriched or depleted within each population were identified using custom microarrays. The genes targeted by shRNAs enriched in EpCAM- cells were identified as candidate regulators of EpCAM expression. This work demonstrates that pooled shRNA libraries may be used in a variety of novel screening strategies, including the identification of novel regulators of tumor-associated genes.

Sponsored by

1:45 Dessert in the Exhibit Hall

 

WORKING BACKWARDS IN CANCER:
FROM THE CLINIC TO DISCOVERY

2:15 Chairperson’s Remarks

Michael Liebman, Ph.D., Managing Director, Strategic Medicine, Inc. 

2:20 Using Drug-Induced Feedback Loops to Identify Indications and Combination Partners

Donald Bergstrom, Director, Experimental Medicine Oncology, Merck

James W. Watters, Associate Director, Molecular Profiling Oncology, Merck

Treatment with molecular targeted agents can result in compensatory feedback regulation as cells respond to inhibition of signaling pathways. We will present clinical evidence that treatment with a small molecule inhibitor of gamma secretase results in pathway modulation and compensatory feedback, and describe pre-clinical experiments designed to leverage this concept for drug response prediction.

2:50 Genomic Solutions to Diagnostic and Prognostic Clinical Predictions in Head and Neck Cancer

Geoffrey Childs, Ph.D., Professor of Pathology, Albert Einstein College of Medicine

Richard V. Smith, M.D., FACS, Professor, Vice-Chair, Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center and Albert Einstein College of Medicine

The strategy our group employs is to utilize the data obtained from high throughput assays including gene expression measurements of mRNA and miRNA, global methylation patterns of DNA and global proteomics to develop prognostic and diagnostic signatures to predict outcome, local regional recurrence presence/absence of lymph node metastasis at initial diagnosis and to predict optimal treatment options.

3:20 Moving Research Closer to the Bedside, in Vitro and in Vivo Analyses with Primary Tumors

Fred Poordad, M.D., Chief of Hepatology, Liver Disease and Transplant Center, Cedars-Sinai Medical Center; Xin Wei Wang, Ph.D., Senior Investigator, Head, Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH; Michael R. Briggs, Ph.D., Senior Director, Biology, Vertex Pharmaceuticals, Inc.

The incidence of Primary Liver Cancer is increasing in the west and constitutes a tremendous burden on world health as the third leading cause of cancer deaths worldwide. The 5 year survival rate is a dismal 11 %, due in large part to late diagnosis and limited treatment options. The etiology of this devastating disease as well as current and proposed new therapies will be discussed. Steps to better diagnose and stratify patients for targeted therapy will be considered as a new and exciting phase of cancer research. Finally, a move toward more relevant research will be presented as an hypothesis that will be tested in the coming years as more new and current therapies are compared and contrasted to current best practice.

4:05 How Do You Go From Pathways to Clinical Outcomes?

Aris Persidis, Ph.D., President, Biovista, Inc.

In drug discovery and development what what really counts is the clinical outcome, the Benefit/Risk of the drug within the context of its pathway or mechanism of action (MoA). Biovista screens the MoA of any drug or target against the MoA of 8,000 indications and 12,000 adverse events (AEs). This is simultaneous, unbiased indication discovery and AE profiling, and it is unique. It helps to bridge the gap from molecular pathway to clinical outcome in a single step. Case studies in cancer and other diseases will be described.

Sponsored by

4:35 Reception in the Exhibit Hall (Sponsorship Available)

5:20 BREAK-OUT DISCUSSIONS in the Exhibit Hall

What is the Forecast for Epigenetics and microRNA?

Moderator: Enal Razvi, Ph.D., System Biosciences SBI

  • Status of the microRNA and epigenetics markets

  • The research market for microRNA and epigenetics: growth and evolution

  •  Diagnostics and therapeutics development based on microRNA and epigenetic signatures

  •  Current challenges and opportunities in these spaces

Challenges to Whole Genome Sequencing

Moderator:  Pauline Ng, Ph.D., Assistant Professor, Genomic Medicine, J Craig Venter Institute

  • Challenges to whole-genome sequencing
  • Identifying de novo and re-current mutations in cancer
  • Addressing tumor heterogeneity
  • How can we move from characterizing gene variation to utilizing the whole genome 
  • Sequencing tumors rather than tumor cell lines
  • The Complex genomic structure of tumor cells: de novo assembly or strategy to detect structural variants

Are there Cancers of Unknown Primary Tumors?

Moderator: Dalia Cohen, Ph.D., Chief Scientific Officer, Rosetta Genomics, Inc.

  • Debate over cancers of unknown primary tumors (CUP)
  • Methods to detect CUPs
  • Consequences of detection of primary

Gene Signatures in Cancer Diagnostics

Co-Moderators: Gary Geiss, Ph.D., Principal Scientist, NanoString Technologies and David Kern, MBA, Director, MyRaQa

  • Developing a gene signature 
  • Validation of gene signatures 
  • Regulatory considerations for gene signature diagnostics 

Systems Chemical Biology-A New Paradigm

Moderator: Ally Perlina, Senior Application Scientist, GeneGo Inc.

  • Utilizing tools for drug repositioning

  • Understanding side effects

  • Understanding the mechanisms of action for drugs

  • Networkable compounds

6:20 Close of Day

 

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2014 Premier Sponsors:

 Elsevier   

 

NanoString 

 

Quanterix 

 

RemedyMD 

 

Singulex 

 

Thomson Reuters