Translational Cancer Medicine
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Friday, September 21
7:30-8:15 am Morning Coffee or Sponsored Breakfast Presentation (Opportunity Available)
Contact Ilana Quigley at email@example.com or 781-972-5457
8:30-8:35 Chairperson’s Opening Remarks
8:35-9:00 Novel Connections between Rho GTPases and Microvesicles in Cancer Progression
Richard A. Cerione, Ph.D., Professor, Molecular Medicine, Cornell University
The roles of microvesicles (MVs) in cancer are receiving a great deal of attention. MV cargo includes receptor tyrosine kinases, cytosolic and nuclear signaling proteins, and RNA transcripts which when transferred to recipient cancer cells, accentuates their transformed properties. Recently, we discovered that MVs isolated from highly aggressive cancer cells confer upon fibroblasts the characteristics of transformed cells. Moreover, we found that different Rho GTPases play important and distinct roles in MV formation and shedding, and that signaling to the metabolic machinery of cancer cells is required for MV biogenesis. These findings shed new light on the potential importance of MVs, as well as Rho GTPases, to cancer progression.
9:00-9:25 Oncogenic Extracellular Vesicles — Biological Effectors and Cancer Biomarkers
Janusz Rak, M.D., Ph.D., Professor, Pediatrics, Montreal Children’s Hospital Research Institute, McGill University
Intercellular trafficking of membrane-derived extracellular vesicles (EVs) represents an intriguing mode of intercellular communication. These processes are altered in cancer, where oncogenic pathways influence the properties and abundance of shed EVs. Notably, EVs mediate extracellular release of mutant proteins and nucleic acids causative for malignant transformation, such as oncogenes and tumor suppressors. Such oncogenic EVs (oncosomes) are taken up by various cells and may trigger transformation-like changes including altered growth, survival angiogenic phenotype, procoagulant conversion, and tumorigenesis. EVs circulating in blood offer unprecedented new access to driver mutations, molecular subtypes, drug targets and other actionable information in cancer.
9:25-9:50 Extracellular Vesicles in Leukemia — Biology and Biomarker Opportunities
Peter Kurre, M.D., Associate Professor, Pediatrics, Oregon Stem Cell Center, Department of Pediatrics and Cell & Developmental Biology, Oregon Health & Science University
Extracellular vesicle trafficking is a constitutive cellular function important to cell-cell communication. Studies confirm that leukemia cells release vesicles rich in protein and RNA cargo. Acute- and chronic myelogenous leukemia vesicles are rich in established biomarkers, including BCR-ABL and Flt3-ITD, respectively, and contain abundant microRNA. Vesicle trafficking promotes proliferative and proangiogenic effects in co-cultured stromal cells. Broadly, extracellular vesicle cargo emerges as a powerful regulator of cell fate in the microenvironment. We propose a mechanistic role for vesicles during leukemogenesis and significant potential for biomarker discovery.
9:50-10:15 The Biology and Clinical Potential of Tumor-Derived Microvesicles
Crislyn D’Souza-Schorey, Ph.D., Professor, Biological Sciences, University of Notre Dame
10:15-11:15 Coffee Break in the Exhibit Hall with Poster Viewing
11:15-11:20 Chairperson’s Opening Remarks
11:20-11:45 Translation of Emerging Biomarkers from Pre-Clinical Species to Human Populations
Jiri Aubrecht, Pharm.D., Ph.D., Senior Director and Safety Biomarker Group Lead, Drug Safety Research & Development, Pfizer
Biomarkers of drug safety provide essential tools for refining of therapeutic index in drug development. Despite the success of routine markers, mainly biochemical parameters used in pre-clinical and clinical settings, a new cohort of safety biomarkers with better sensitivity and specificity is being considered. Since drug development relies on pre-clinical evaluation of lead compounds, the evaluation of translation across animal species including to humans is essential. In this presentation, case studies documenting recent advances in cross species translation for biomarkers of hepatotoxicity and nephrotoxicity will be provided.
11:45-12:10 pm New Safety Biomarkers on the Horizon: The IMI SAFE-T Consortium
Michael Merz, M.D., Director, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research
The EU’s IMI SAFE-T consortium is a public/private partnership of 25 organizations from the pharmaceutical industry, small- to medium-sized enterprises, academic institutions and clinical units of excellence with representatives from health authorities as external observers and advisors. The key objective of the five-year project is clinical qualification of biomarkers for drug-induced kidney, liver and vascular injury in translational studies and obtaining regulatory acceptance in translational and clinical contexts. The talk will give an overview on the consortium, the qualification program, and the biomarker candidates. Preliminary data from the exploratory qualification phase will be presented for some selected biomarkers.
12:10-12:35 Progression of Biomarkers for Alzheimer’s Disease
Johan Luthman, D.D.S., Ph.D., Senior Program Leader, Neuroscience and Ophthalmology Research & Development, Merck & Co., Inc.
12:35 Close of Conference
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