Track 3: Advancing Cancer Therapy
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THURSDAY, SEPTEMBER 24
Chairperson's Opening Remarks
Chairperson to be Announced
11:30-12:00 Accurate Quantitation of Circulating Tumor Cells with Low Molecular Weight Tumor-Targeted Fluorescent Dyes
Philip S. Low, Ph.D., Ralph C. Corley Distinguished Professor, Department of Chemistry, Purdue University
We have developed both in vivo and in vitro methods for detecting low numbers of circulating tumor cells (CTCs). The first method involves injecting the cancer patient with a fluorescent conjugate of a low molecular weight tumor-specific ligand (e.g. folate, DUPA, etc.) and using a multiphoton fluorescence microscope to quantitate CTCs as they flow through a near surface vein of the patient. In this method, the patient’s bloodstream is used as a flow cytometer, and the entire blood volume of the patient can eventually be analyzed. The second method involves addition of the same tumor-specific fluorophore to a 2 ml sample of the cancer patient’s blood ex vivo. After removing erythrocytes, the sample is analyzed for CTCs by conventional flow cytometry. Clinical and preclinical data on both methods using two separate tumor-targeted fluorescent dyes will be presented.
12:00-12:30 In Vivo Detection of Circulating Tumor Cells in Lymphatics as an Earliest Marker of Metastasis
Ekaterina Galanzha, Ph.D., Assistant Professor, University of Arkansas for Medical Sciences
Compared to blood cancer tests, the assessment of circulating (disseminated) tumor cells (CTCs) in lymphatics is not well established. We introduce a novel, ultra-sensitive method using a flow cytometry schematic for in vivo, non-invasive photoacoustic lymph testing for cancer cells directly in lymph flow. This assay is based either on label-free counting of CTCs with over-expressed intrinsic biomarkers or on using functionalized gold nanoparticles as high contrast photoacoustic molecular multicolor agents. The study on tumor-bearing mouse models demonstrated quantification of CTCs within lymphatics in vivo with a threshold sensitivity of one metastatic cell among millions of normal cells. These preclinical studies, after further development, may provide a new form of medical diagnostic testing of the lymphatics that could be supplementary to blood cancer testing.
12:30-2:00 Lunch on your own
2:00-2:30 Use of Biomarkers and Translational Science to Accelerate and Improve Oncology Drug Development: Opportunities and Roadblocks
J. Carl Barrett, Ph.D., Vice President and Global Head, Oncology Biomarkers and Imaging, Oncology Translational Medicine, Novartis Institutes of BioMedical Sciences, Inc.
The steps in oncology drug development in patients include: optimizing dose-schedule, predicting patients that will respond, detecting tumor responses rapidly for proof-of-concept trials, using surrogate endpoints for disease monitoring, assuring safety of drug therapy, and developing rational-based combination therapies. Biomarkers are pivotal in meeting each of these challenges. A general strategy for using biomarkers in oncology drug development will be presented and includes: having a systematic biomarker plan for each new agent that is consistent, science-based and focused using common standards for assays and data; building a biomarker tool kit with analytically and clinically validated biomarker assays; building on clinical experience (positive and negative) and execution excellence involving a team effort (physicians, clinical staff, biomarker experts and data management) and building a strong partnership between Novartis and its clinical investigators.
2:30-3:00 Enabling Personalized Medicine through Application of Biomarkers in Clinical Development
Nicholas C. Dracopoli, Ph.D., Vice President, Biomarkers, Centocor Research & Development, Johnson & Johnson
The observer effect describes the changes that the act of observation will make on the phenomenon being observed and has many applications in the physical and experimental sciences. In drug development, if we consider biomarkers as the observer and the clinical trial as the phenomenon, we can ask how the process of analyzing biomarkers impacts the clinical trial process. It is clear that the simple act of collecting biopsies, let alone completing complex bioanalytical studies of these samples, impacts the ability to run clinical trials quickly and economically. Consequently, it is necessary to demonstrate that the value derived from the observation exceeds the cost to the phenomenon. This presentation will discuss how different types of biomarkers can be used during the drug development process to increase probability of success in the successive stages of drug discovery and development, and support decisions for further investment in subsequent development phases. Several examples of biomarker applications to confi rm mechanism of action, explore PK/PD interactions and to derive predictive markers in ongoing drug development programs will be described.
3:00-4:00 Networking Refreshment Break with Poster and Exhibit Viewing
4:00-4:30 Multicenter Phase III Clinical Trial Validation of Circulating Tumor Cells in Blood as Prognostic Biomarkers in Melanoma Patients Receiving Immunotherapy
Dave S.B. Hoon, Ph.D., Department of Molecular Oncology, John Wayne Cancer Institute, Saint John’s Health Center
Melanoma is often an aggressive disease with poor prognosis when metastasis occurs, although some patients have better outcome than others in treatment responses. Identification of these patients will help improve overall survival. Development of new therapeutics and monitoring patients during treatment requires critical assessment of patients with efficient blood biomarkers to identify those patients with good and poor prognosis. Circulating tumor cells (CTC) are a form of blood biomarkers that can potentially identify prognosis in patients. In a recently completed Phase III international multicenter clinical immunotherapy trial we validated mRNA CTC biomarkers in correlation with disease outcome. CTC biomarkers before treatment as well as during treatment were significantly prognostic of disease-free and overall survival in AJCC stage IV melanoma patients. This presentation will discuss an international study that demonstrated the utility of CTC blood biomarkers.
4:30-5:00 The Clinical Utility of Circulating Tumor Cell Analysis: What Have We Learned So Far?
Beverly C. Handy, Ph.D., Assistant Professor, Clinical Chemistry, Department of Laboratory Medicine, The University of Texas, M.D. Anderson Cancer Center
Metastatic cancers, even when of the same tissue type, show considerable variability in their clinical behavior. Prognostic indicators that are of proven value in predicting disease aggressiveness and response to therapy are, therefore, extremely useful aides for optimizing individual treatment planning. Among these, a growing body of literature indicates that the enumeration of circulating tumor cells (CTC) from peripheral blood can serve as an independent prognostic marker for clinically managing patients with some types of metastatic cancers. In particular, the level of CTC has been shown to be predictive of survival in breast, colorectal, and prostate metastatic disease. It is likely that it will be useful in tumors of other organs as well. Additional potential applications include evaluation of treatment response and use in disease staging. Isolation of CTC also offers potential opportunities for further analysis and molecular characterization of these cells, which may allow further optimization of treatment.
5:00-5:30 Circulating Tumor Cells as Markers of Disease Progression
Peter Kuhn, Ph.D., Associate Professor, Cell Biology, The Scripps Research Institute
Circulating tumor cell enumeration and characterization have the potential of providing real-time access to epithelial cancers in patients. Presented will be results from a small series case study in non-small cell lung cancer patients for which CTC analysis is compared with clinical progression. Morphologic and molecular characterization at the single cell level will be discussed in the context of the data set and in the context of individual patient management.
5:30 Close of Day