OCT 17, 2013 11:00 AM PDT

The Need for Critical Reassessment of Current Strategies for Cancer Therapeutics.

  • Chief Scientist, Complex Adaptive Systems, Regents' Professor and Del E. Webb Chair in Health I, Arizona State University
      Dr. George Poste is Chief Scientist, Complex Adaptive Systems Initiative (CASI), Regents Professor and Del E. Webb Chair in Health Innovation at Arizona State University. He assumed this post in February 2009. This program links expertise across the university in research on synthetic biology, ubiquitous sensing and healthcare informatics for personalized medicine. He founded the Biodesign Institute at ASU and served as Director for 2003 to 2009. In creating this Institute, Dr. Poste designed and built 400,000 sq. ft. of new facilities, achieved cumulative research funding of $300 million and recruited over 60 faculty, including three members of the National Academies of Science and Engineering. He serves on the Board of Directors of Monsanto (since 2003), Exelixis (since 2004), Caris Life Science (since 2005), and the Scientific Advisory Board of Synthetic Genomics (since 2009). From 1992 to 1999 he was Chief Science and Technology Officer and President, R&D of SmithKline Beecham (SB). During his tenure at SB he was associated with the successful registration of 31 drug, vaccine and diagnostic products. In 2004 he was named as R&D Scientist of the Year by R&D Magazine, in 2006 he received the Einstein award from the Global Business Leadership Council and in2009 received the Scrip Lifetime Achievement award voted by the leadership of the global pharmaceutical industry. He has published over 350 research papers and edited 14 books on pharmaceutical technologies and oncology. He has received honorary degrees in science, law and medicine for his research contributions and was honored in 1999 by HM Queen Elizabeth II as a Commander of the British Empire for his contributions to international healthcare and security. He is a Fellow of the Royal Society, the Royal College of Pathologists and the UK Academy of Medicine, a Distinguished Fellow at the Hoover Institution, Stanford University and a member of the Council for Foreign Relations. He served as a member of the Defense Science Board from 2003 to 2009 and Health Board of the US Department of Defense (DoD) and is currently a member of the US Institute of Medicine Board on Global Health. He has served as a member of Advisory Committees for multiple U.S. Government Agencies in areas of defense, national security and healthcare. Abstract:


    Curative therapy for metastatic disease in solid malignancies remains frustratingly elusive due to the long recognized problem of tumor cell heterogeneity and emergence of treatment resistant lesions. Cancer is a complex adaptive system. Tumor progression reflects the co-evolutionary dynamics of host-tumor interactions and the progressive selection of tumor clones of increasing fitness able to survive in varied host tissue microenvironments and to circumvent host defenses and therapeutic intervention. Improved success in confronting this intrinsic biological complexity requires major changes in current approaches to the discovery and clinical validation of new therapeutics. The following needs must be accorded higher priority. *new tools to map the dynamic topology of perturbed molecular signaling networks in malignancies arising in different cell lineages to better predict the compensatory pathways most likely to confer resistance to guide new drug development and as companion diagnostics for monitoring emergence of resistance *new approaches for therapeutic action at multiple targets in perturbed signaling networks via new combinations of targeted therapies or, more challenging, the design of promiscuous polypharmacology in a single agent *new minimally invasive blood-based diagnostics such as CTCs, ctDNA or exosomes for faster detection of resistance and agile changes in treatment regimens *new adaptive clinical trial protocols such as I-SPY for simultaneous evaluation of multiple agents and agile switching of agent combinations guided by biomarker profiling of response/resistance patterns. This will also require new regulatory paradigms to accommodate the increased statistical and logistical complexities of adaptive clinical trials and efficacy assessment of combinations of investigational agents and companion biomarkers *new value propositions for payors (and patients) linking reimbursement and pricing policies to more substantial improvements in clinical outcomes *new approaches for rapid updating of standard-of-care (SOC) guidelines and improved physician education to reflect advances in molecular oncology and greater adoption of routine molecular profiling of patients for improved therapy selection *new patient advocacy approaches to enhance patient education about the value of molecular profiling in treatment choice and increase the enrollment of eligible patients into investigational trials

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