Group 5 Biomarkers & Chemoprevention: Where are we? March 4th/5th 2016 Miriam Rosin PhD Director, BC Oral Cancer Prevention Program, BC Cancer Agency GOCF Organizing Committee and Co-Chair, Group 5 Contact: [email protected] Risk prediction for dysplasia progression in developed countries Sok Ching Cheong, PhD Group Leader, Oral Cancer Research Programme, Cancer Research Malaysia Adjunct Professor, University of Malaya, Malaysia. Contact: [email protected] What can be done now in less developed countries Anil K Chaturvedi, PhD Investigator, Division of Cancer Epidemiology and Genetics National Cancer Institute Contact:[email protected] Natural history of OPMDs & biomarkers: The establishment of national and regional programs J. Silvio Gutkind, PhD Associate Director of Basic Science, UC San Diego Moores Cancer Center GOCF Organizing Committee and Co-Chair, Group 5 Contact: [email protected] Oral Cancer Prevention in the Era of Precision Medicine Scott Lippman, MD Director, UC San Diego Moores Cancer Associate Vice Chancellor for Cancer Research and Care Contact: [email protected] Contributor to white paper Eva Szabo, MD Chief, Lung and Upper Aerodigestive Cancer Research Group Division of Cancer Prevention, National Cancer Institute Contact: [email protected] Discussant Paul Brennan Head of Genetic Section International Agency for Research on Cancer Contact: [email protected] Moderator Risk prediction for dysplasia progression in developed countries Miriam P Rosin, PhD Director, BC Oral Cancer Prevention Program BC Cancer Agency Evolution of Biological Framework Evolution of a comprehensive progression biomarker set • Increased capacity to share knowledge & to craft new technology • What information do we collect? • How do we collect this information? • How do we share in process of creating knowledge? • Focus of collection – depth & breadth Pure Nature’s Photos. Facebook The need to look at the broader picture Variation in natural history of disease in different settings Universal vs specific to setting If yes, then what? Pictures from a biomarker/chemoprevention trial in Usbekistan in 1984. Nass users given multi-vitamin treatment Evolution of progression models “Battle of the Clones” OPMD Invasive carcinoma Superficial Intermediate •Self-sufficiency in growth signals •Insensitivity to antigrowth signals Parabasal •Evading apoptosis Basal •Limitless replicative potential Basement •Sustained angiogenesis membran •Tissue invasion and metastasis e Fibroblast Blood vessel Inactivation of 9p21 Apoptosis (genetic / epigenetic Senescence Progression mutations, viral oncogenes) Genomic instability Cell cycle deregulation Heterogeneity – Impact of technology / new knowledge how many ways to • Detailed understanding of genetic change in clones, single cells end-game • Processes outside the clones / lesion, changing over time • Developmental windows (sets of genes on / off, induced by exposure) • Stressors, especially systemic, physiologic or tissue level with age • Protectors (micro-environment, normal cells), e..g immune system • Cross over studies, different cancers, chronic diseases: markers, processes, drugs Rosin et al., 2000; Kensler 2016 BC model of integration of dental & medical systems Readiness of Dental Clinics •Fluorescence Visualization Back to community Dental •Demographics • Guidelines Health •Risk Factors • Protocols Professions •Clinical • Referral pathway • Capacity building • Switching norms • Biopsyg • Social marketing Specialists • Histology Surveillance System Oral Biopsy • Cytology Service • QP • Register patients • Monitor patient flow Next • Outcome •Assessment Generation Clinic Oral Cancer Prediction Longitudinal Study BC Cancer Agency (Primary dysplasia 10-15 yrs) Today focus on mild and moderate dysplasia • Treatment How to help patients now? Concept of Triage INFA-Arf region on 9p 21 3 2 1α 1β 2 1 Human 9p21 D9S1751 D9S1748 D9S171 21,550K 21,950K 22,000K 24,500K 24,550K ARF p16INK4a p15INK4b CDK4 p16/CDKN2A MDM2 p53 p21 Cyclin D p14/ARF p15/CDKN2B P RB RB Cell Cycle E2F Apoptosis E2F Progression Senescence • Test: 9p21 a “gatekeeper” – 1st separation • Combined with change to markers on 2 other critical sites on 4q and 17p => Separate out high-risk (HR) cases - Genome marker based technology (gMART) 10