FAST Congress

 

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THURSDAY, SEPTEMBER 16

7:00 am Registration Open

8:00-8:30 Morning Coffee

 

Targeted Cancer Therapy

8:25-8:30 Chairperson’s Opening Remarks

8:30-9:00 Rare Cancers: A Paradigm for Precision Medicine

Glen Weiss, M.D., Co-Head, Lung Cancer Unit, Translational Genomics Research Institute (TGen); Director, Thoracic Oncology, TGen Clinical Research Services at Scottsdale Healthcare

In this presentation, I will show why the application of Precision (Personalized) Medicine to treat patients with rare cancers is important. The presentation will highlight the identification of the Hedgehog Pathway, how discovery of this pathway led to development of novel agents that target it, and published clinical results of at least one of these Hedgehog pathway inhibitors that demonstrated promising clinical benefit and published in the New England Journal of Medicine (Sept 2009). The talk will also cover what was learned from this real life example could be applied to other rare and common cancers, and current barriers that need to be dealt with to realize this potential.

9:00-9:30 Molecular Insight into Metastatic Potential and Response to Tamoxifen in Breast Cancer

Andrew Grupe, Ph.D., Senior Director, Pharmacogenomics Research & Development, Celera Diagnostics

Prognostic expression signatures can aid in selecting the most appropriate treatment regimen relative to the expected course of disease. Expression signatures with different gene sets have been shown to have similar performance. Correlating breast cancer
signatures with drug response in widely used cell lines that model human tumors provides a test system to assess the predictive power of these signatures for novel therapeutics during the early stages of drug development. Here we will describe a signature that is prognostic of distant metastasis formation and predictive of tamoxifen treatment in breast cancer patients. Furthermore we will describe correlation with other reported signatures, thereby suggesting similar clinical utility.

9:30-10:00 Comprehensive Profiling of EGFR/HER Receptors

Nita Maihle, Ph.D., Professor, Ob/Gyn & Reproductive Sciences and Pathology, Yale University School of Medicine

While EGF/HER receptors are clinically validated targets in cancer therapy, the success of this new biologically-targeted therapeutics has been limited by our inability to accurately predict which patients will respond to therapy. New evidence suggests that this problem is caused at least in part, by our failure to incorporate the complexities of regulation of this receptor family in the development of these assays, and specific examples of improvements based on comprehensive profiling of EGF/HER receptor expression will be presented.

10:00-10:30 Networking Coffee Break

 

Biomarkers for Cancer Patient Selection

10:30-11:00 CAIX: A Biomarker for Hypoxia and a New Tool for Selecting and Monitoring Patients Receiving CAIX Targeted Therapies

Walter P. Carney, Ph.D., Head, Oncogene Science, Siemens Healthcare Diagnostics, Inc.

Carbonic anhydrase (CAIX) is a transmembrane oncoprotein with an extracellular domain that is highly expressed in a variety of cancers and induced by hypoxia. Studies have shown that the state of hypoxia correlates very well with resistance to radiation and chemotherapies and thus a biomarker for hypoxia, such as CAIX, could be important for guiding therapies. The surface location of CAIX allows quantitation by IHC, ELISA or imaging. We have developed both a CAIX IHC test as well as a CAIX ELISA test that could be used as companion diagnostic in clinical trials of CAIX targeted drugs. Quantitation of CAIX by IHC in tumor tissue and quantitation of the circulating levels of CAIX by ELISA may be used to identify patients with CAIX positive tumors for radiation/chemotherapy decisions. The CAIX hypoxia biomarker tests may also be used to select patients for CAIX targeted therapies, to monitor the efficacy of CAIX targeted therapies or to predict clinical outcomes from CAIX targeted therapies. The combination of an IHC test and ELISA test will allow continuous monitoring of patients from initial diagnosis to early detection of recurrence of CAIX positive tumors.

11:00-11:30 Drug Signaling Network-Based Biomarkers for Colorectal Cancer Patient’s Response to Cetuximab

Jae K. Lee, Ph.D., Director and Associate Professor, Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia School of Medicine

In this study we demonstrate that drug signaling network-based biomarker prediction models can not only predict patients’ therapeutic responses but also provide more direct insight on drug signaling gene-network activities of individual patients. First, in vitro drug activity and gene expression data of 60 NCI and 106 GSK cancer cell lines were used to identify drug sensitivity biomarkers for EGFR inhibitor. Known functional biomarkers related to this drug’s molecular mechanisms of action were obtained from literature and then examined and filtered for their expression correlations with each drug activity using the above cell line data. The gene network-based model of EGFR inhibitor was then made with its 16 drug-signaling networks based on these two biomarker sets. Independent prediction scores of this model on 43 colorectal cancer patients who were treated with cetuximab and K-RAS wild were significantly associated with their clinical responses and outcomes.

11:30-12:00 pm Combination of the Biomarker TOP2A and TIMP-1 Identify the Majority of Breast Cancer Patients Responding to Treatment with Anthracyclines

Kirsten Vang Nielsen, Ph.D., Senior Principal Scientist, Research & Development, Dako A/S

HER2 (Human epidermal growth factor receptor 2), TOP2A (topoisomerase II alpha) and TIMP-1 (tissue inhibitor of matrix metalloproteinase 1) have all been identified as biomarkers that can predict the treatment outcome associated with anthracycline-containing chemotherapy. By screening for TOP2A and TIMP-1 in combination, nearly twice as many patients classified as anthracycline responsive were identified compared with using the biomarkers individually. TOP2A is measured by the FISH pharmDx™ Kit developed by Dako and TIMP-1 by IHC.

12:00-12:30 SPDEF and SPDEF Induced Biomarkers for Bridging Cancer Diagnosis, Prognosis and Drug Development

Ashwani Sood, Ph.D., Member and Assistant Professor, Oncology, Department of Microbiology and Immunology, SUNY at Buffalo, Roswell Park Cancer Institute

SPDEF is frequently over expressed during breast and prostate cancer progression. SPDEF expression is induced following activation of androgen receptor; and transfection of SPDEF enhances tumorigenicity in immunodeficient mice High SPDEF expression predicts poor overall survival in breast cancer patients and early cancer recurrence in prostate cancer patients. SPDEF expression is detected in circulating breast tumor cells. SPDEF is immunogenic and anti-SPDEF immunity delays mammary tumor development in mice.

12:30 Close of Conference