eBriefing

Personalized Medicine: A Search for Tailored Therapeutics

Personalized Medicine
Reported by
Abbas Abdollahi

Posted December 13, 2011

Overview

The goal of personalized medicine is to identify the disease state of each patient and to implement therapeutic methods or strategies that are unique to that individual. On September 20, 2011, the Biochemical Pharmacology Discussion Group of the New York Academy of Sciences, and the New York Chapter of American Chemical Society held a symposium on this topic titled Personalized Medicine: A Search for Tailored Therapeutics. The researchers in this field presented recent insights and advances and provided clinical models and pilot studies that are underway. They described non-invasive techniques that are highly sensitive and capable of analyzing large genomic regions or loci, as well as being more cost effective. The need for accurate pathophysiological network models that can lead to discovery of more specific and sensitive disease markers for targeted therapy was also highlighted at the symposium. Finally, researchers discussed the emerging role of epigenetic regulation in personalized medicine and the influence of specific gene mutations in tumors on drug response in individual patients.

Use the tabs above to find a meeting report and multimedia from this event.

Presentations available from:
Charles R. Cantor, PhD (Sequenom, Inc.)
Mark R. Chance, PhD (Case Western Reserve University)
Randy L. Jirtle, PhD (Duke University Medical Center)
Marc Ladanyi, MD (Memorial Sloan-Kettering Cancer Center)


Presented by

  • American Chemical Society, New York Chapter
  • The New York Academy of Sciences

For a full list of sponsors, please view the Sponsorship tab.

Websites

Molecular Testing at Memorial Sloan-Kettering Cancer Center
A description of molecular testing at MSKCC for determining the most effective treatments for non-small cell lung cancer.

Personalized Medicine Coalition
The Personalized Medicine Coalition (PMC), was launched in 2004 to educate the public and policymakers, and to promote new ways of thinking about health care.

National Comprehensive Cancer Network
The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 21 of the world's leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system.

Network Biology Resources
Network Biology Resources is an annotated but not complete catalog of publications on disease models and computational model building and testing.

The Pharmacogenomics Journal
The Pharmacogenomics Journal is dedicated to the rapid publication of original research on basic pharmacogenomics research and its clinical applications.


Journal Articles

Charles R. Cantor

Nygren AO, Dean J, Jensen TJ, et al. Quantification of fetal DNA by use of methylation-based DNA discrimination. Clin Chem. 2010;56(10):1627-1635.

Harris TJ, McCormick F. The molecular biology of cancer. Nat. Rev. Clin Oncol. 2010;7:251-265.

Thomas RK, Baker AC, Debiasi RM, et al. High-throughput oncogene mutation profiling in human cancer. Nat. Genet. 2007;39(3):347-351.

Fumagalli D, Gavin PG, Taniyama Y, et al. A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes. BMC Cancer 16;10:101.

Ehrich M, Deciu C, Zwiefelhofer T, et al. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am. J. Obstet. Gynecol. 2010;204(3):205.e1-11.

Lo YM, Chan KC, Sun H, et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci. Transl. Med. 2010;2(61):61ra91.

Chiu RW, Cantor CR, Lo YM. Non-invasive prenatal diagnosis by single molecule counting technologies. Trends Genet. 2009;25(7):324-31.

Lo YM, Lun FM, Chan KC, et al. Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proc. Natl. Acad. Sci. USA 2007;104(32):13116-21.

Mark R. Chance

Verhaak RG, Hoadley KA, Purdom E, et al. An integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR and NF1. Cancer Cell 2010;17(1):98-110.

Bebek G, Koyutürk M, Chance MR, Price ND. Integrative-Omics for translational science: Session Introduction. Pac. Symp. Biocomput. 2011;1-3.

Chowdhury SA, Nibbe RK, Chance MR, Koyutürk MJ. Sub-network state functions define dysregulated sub-networks in cancer. Comput. Biol. 2011;18(3):263-281.

Linderman GC, Patel VN, Chance MR, Bebek G. BiC: a web server for calculating bimodality of coexpression between gene and protein networks. Bioinformatics 2011;27(8):1174-1175.

Nibbe RK, Chowdhury SA, Koyutürk M, Ewing R, Chance MR. Protein–protein interaction networks and sub-networks in the biology of disease. Wiley Interdiscip. Rev. Syst. Biol. Med. 2011;3(3):357-367.

Nibbe RK, Markowitz S, Myeroff L, Ewing R, Chance MR. Discovery and scoring of protein interaction sub-networks discriminative of late stage human colon cancer. Mol. Cell Prot. 2009;8(4):827-845.

Ideker T, Sharan R. Protein networks in disease. Genome Res. 2008;18(4):644-652.

Chuang HY, Lee E, Liu YT, Lee D, Ideker T. Network-based classification of breast cancer metastasis. Mol. Syst. Biol. 2007;3(140):1-10.

Randy L. Jirtle

Abel KM, Allin MP, Jirtle RL. Schizophrenia, cancer and imprinting: early nutritional influences. Br. J. Psychiatry 2006;188:394.

Bell AC, Felsenfeld G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 2000;405(6785):482-485.

Dolinoy DC, Das R, Weidman JR, Jirtle RL. Metastable epialleles, imprinting, and the fetal origins of adult diseases. Pediatr. Res. 2007;61(5 Pt 2):30R-37R.

Dolinoy DC, Huang D, Jirtle RL. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc. Natl. Acad. Sci. USA 2007;104(32):13056-13061.

Dolinoy DC, Jirtle RL. Environmental epigenomics in human health and disease.Environ. Mol. Mutagen. 2008;49(1):4-8.

Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ. Health Perspect. 2006;114(4):567-572.

Hoek HW, Brown AS, Susser E. The Dutch famine and schizophrenia spectrum disorders. Soc. Psychiatry Psychiatr. Epidemiol. 1998;33(8):373-379.

Hoyo C, Murtha AP, Schildkraut JM, et al. Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy. Epigenetics 2011;6(7):928-936.

Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat. Rev. Genet. 2007;8(4):253-262.

Jirtle RL, Sander M, Barrett JC. Genomic imprinting and environmental disease susceptibility. Environ. Health Perspect. 2000;108(3):271-278.

Murphy SK, Jirtle RL. Imprinted genes as potential genetic and epigenetic toxicologic targets. Environ. Health Perspect. 2000:108 Suppl 1:5-11.

Nolan CM, Killian JK, Petitte JN, Jirtle RL. Imprint status of M6P/IGF2R and IGF2 in chickens. Dev. Genes Evol. 2001;211(4):179-83.

Ravelli ACJ, van der Meulen JHP, Michels, RPJ, et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet 1998;351(9097):173-177.

Surani MA, Barton SC, Norris ML. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 1984;308(5959):548-550.

Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 2004;20(1):63-68.

Waterland RA, Jirtle RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell Biol. 2003;23(15):5293-5300.

Weidman JR, Dolinoy DC, Murphy SK, Jirtle RL. Cancer susceptibility: epigenetic manifestation of environmental exposures. Cancer J. 2007;13(1):9-16.

Marc Ladanyi

Arcila ME, Oxnard GR, Nafa K, et al. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin. Cancer Res. 2011;17(5):1169-1180.

Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J. Clin. Oncol. 2011;29(21):2866-2874.

Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to geftinib. N. Engl. J. Med. 2004;350(21):2129-2139.

Maheswaran S, Sequist LV, Nagrath S, et al. Detection of EGFR mutation in circulating lung-cancer cells. N. Engl. J. Med. 2008;359(4):366-377.

Mok TS, Wu YL, Thongprasert S, Yang CH, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 2009;361(10):947-57.

Oxnard GR, Arcila ME, Chmielecki J, Ladanyi M, et al. New strategies in overcoming acquired resistance to epidermal growth factor tyrosine kinase inhibitors in lung cancer. Clin. Cancer Res. 2011;(17):5530-5537.

Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304(5676):1497-500.

Paik PK, Arcila ME, Fara M, Sima CS, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J. Clin. Oncol. 2011;(15)29:2046-2051.

Pao W, Iafrate AJ, Su Z. Genetically informed lung cancer medicine. J. Pathol. 2010;223(2):230-240.

Pao W, Kris MG, Iafrate AJ, et al. Integration of molecular profiling into the lung cancer clinic. Clin. Cancer Res. 2009;15(17):5317-5322.

Pao W, Ladanyi M. Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method. Clin. Cancer Res. 2007;13(17): 4954-4955.

Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc. Natl. Acad. Sci. USA, 2004;101(36):13306-13311.

Pao W, Miller VA, Politi KA. et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005;2(3):e73.

Riely GJ, Ladanyi M. KRAS Mutations: an old oncogene becomes a new predictive biomarker. J. Mol. Diagn. 2008;10:493-495.

Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448(7153):561-566.

Taylor BS, Ladanyi M. Clinical cancer genomics: how soon is now? J. Pathol. 2011;223(2):318-326.

Organizers

Ann del Campo, MS, PhD

Sequenom, Inc.
e-mail

Ann del Campo received her BS degree in biology and chemistry from St. Joseph College in West Hartford, CT, in 1977 and completed her MS and PhD degree in experimental pathology from the University of Southern California LAC-USC Medical Campus in 1984. Following work at Cedars-Sinai Medical Center in Beverly Hills, CA, she joined industry and was quickly recognized as an "ambassador" to work with other company representatives in industry who needed technical expertise and marketable presentations. In 1989, she joined Amersham Life Sciences and then GE Healthcare for an 18-year tenure bringing new technologies to market, including proteomics, high-throughput screening, custom preparations for ADME, and live cell imaging technologies within pharmaceutical companies and academic centers of excellence. During this time she received numerous awards for excellence in industry. Del Campo is currently a senior business development manager at Sequenom, Inc., and works with well-recognized scientists in translational sciences and biomarker validation studies to enable more tailored health care treatments for patients in oncology and other diseases where genomic signatures can enable improved outcomes. She has served as a member of the Society for Laboratory Automation and Screening's Education Advisory Committee and is working in her local community to promote student mentorship programs with local schools to engage students and their families in healthier lifestyles by connecting them to local farms.

Charles A. Lunn, PhD

Merck Research Laboratories
e-mail

Charles A. Lunn received his BA and PhD degrees from Johns Hopkins University in Baltimore, MD, in 1985. Following postdoctoral training at SUNY Stony Brook, he joined Schering-Plough's Department of Immunology, with a focus on novel immune modulators. He joined the New Lead Discovery group at Schering-Plough in 2004 and retained this position when Schering-Plough and Merck merged in 2009. Lunn's 50 publications include editing the book Membrane Proteins as Drug Targets, part of Elsevier's Progress in Molecular Biology and Translational Science series. He is currently a research fellow with the department of In Vitro Pharmacology at Merck Research Laboratories in Kenilworth, NJ. Lunn is also program coordinator for the Biochemical Pharmacology Steering Committee at the New York Academy of Sciences and a member of the Society for Laboratory Automation and Screening's Education Advisory Committee.

Jennifer Henry, PhD

The New York Academy of Sciences
e-mail

Jennifer Henry received her PhD in plant molecular biology from the University of Melbourne, Australia, with Paul Taylor at the University of Melbourne and Phil Larkin at CSIRO Plant Industry in Canberra, specializing in the genetic engineering of transgenic crops. She was then appointed as Associate Editor, then Editor, of Functional Plant Biology at CSIRO Publishing. She moved to New York for her appointment as a Publishing Manager in the Academic Journals division at Nature Publishing Group, where she was responsible for the publication of biomedical journals in nephrology, clinical pharmacology, hypertension, dermatology, and oncology.Henry joined the Academy in 2009 as Director of Life Sciences and organizes 35–40 seminars each year. She is responsible for developing scientific content in coordination with the various life sciences Discussion Group steering committees, under the auspices of the Academy's Frontiers of Science program. She also generates alliances with outside organizations interested in the programmatic content.


Speakers

Charles R. Cantor, PhD

Sequenom Inc.
e-mail | website | publications

Charles Cantor is a founder and Chief Scientific Officer at SEQUENOM, Inc., a genetics discovery company with tools, information, and strategies for determining the medical impact of genes and genetic variations. He is also founder of SelectX Pharmaceuticals, a drug discovery company; Retrotope, an anti-aging company; and Dithera, a biotherapeutic company. Cantor is professor emeritus in biomedical engineering and pharmacology and was the director of the Center for Advanced Biotechnology at Boston University. He is adjunct professor of bioengineering at the University of California San Diego, adjunct professor of molecular biology at the Scripps Institute for Research, and distinguished adjunct professor of physiology and biophysics at the University of California Irvine. Prior to this, Cantor held positions at Columbia University and the University of California at Berkeley. He was also the director of the Human Genome Center Project of the Department of Energy at Lawrence Berkeley Laboratory. Cantor has been granted 60 U.S. patents and wrote a three-volume textbook on biophysical chemistry. He coauthored the first textbook on genomics, titled The Science and Technology of the Human Genome Project. In addition, he sits on the advisory boards of more than 15 national and international biotechnology firms, has published more than 450 peer-reviewed articles, and is a member of the National Academy of Sciences.

Mark R. Chance, PhD

Case Western Reserve University
e-mail | website | publications

Mark Chance is professor of general medical sciences, Director of the Center for Proteomics and Bioinformatics, and professor and interim chair of the Department of Genetics at the Case Western Reserve University School of Medicine. Chance received his PhD in biophysics from the University of Pennsylvania in 1986. He spent a large portion of his career teaching at the Albert Einstein College of Medicine prior to joining the Case Western Reserve University School of Medicine and the Center for Proteomics and Bioinformatics in 2005. The Chance lab uses quantitative mass spectrometry and 2-D gel techniques in order to identify biomarkers and regulatory pathways in complex diseases such as cancer, diabetes, and HIV infection. A major emphasis is placed on applying state-of-the art proteomics and systems biology tools to investigate HIV pathogenesis in the context of drug abuse, and provide significant biomarkers of cancer progression and response to therapy. The use of high-resolution mass spectrometry instruments of the Center, coupled with the advanced bioinformatics and biostatistical pipelines for analysis, provide quantitative label free protein expression analysis using a "shotgun" proteomics approach. Subsequent analysis using network and pathway tools provide novel insights into patho-physiological changes in disease. Chance has received numerous awards, including the Upjohn Company New Faculty Research Award and the Irma T. Hirschl Career Scientist Award. He has also published over 200 manuscripts on his proteomics, mass spectrometry, and bioinformatics research.

Randy L. Jirtle, PhD

Duke University Medical Center
e-mail | website | publications

Randy L. Jirtle is a professor of radiation oncology and an associate professor of pathology at Duke University, Durham, NC, where he has been a faculty member since 1977. He graduated with a BS degree in nuclear engineering in 1970 and a PhD degree in radiation biology in 1976, both from the University of Wisconsin-Madison. Jirtle's research interests are in epigenetics, genomic imprinting, and the fetal origins of disease susceptibility. Jirtle holds two U.S. patents on imprinted genes, and another one is pending approval. He has published over 170 peer-reviewed articles, including 10 publications featured on journal covers. He was also a featured scientist on the NOVA and ScienceNow television programs on epigenetics and on National Public Radio programs The People's Pharmacy, The DNA Files, SQ Radio, and The Leonard Lopate Show: Please Explain. He has delivered numerous endowed lectures and was invited to present his research at the 2004 Nobel Symposium on Epigenetics. He was honored in 2006 with the Distinguished Achievement Award from the College of Engineering at the University of Wisconsin–Madison. In 2007 Jirtle received an Esther B. O'Keeffe Charitable Foundation Award and capped off the year with a nomination for Time Magazine's Person of the Year. He was the inaugural recipient of the Epigenetic Medicine Award in 2008 and received the STARS Lecture Award in Nutrition and Cancer from the National Cancer Institute in 2009. In 2010 he was invited to participate in the launch meeting of the International Human Epigenome Consortium (IHEC) in Paris, the Aspen Ideas Festival in Colorado, and Nestlé's Seventh International Nutrition Symposium in Switzerland. Jirtle was invited this year to speak at the Epigenomics in Clinical Medicine Symposium sponsored by The Nobel Assembly at Karolinska Institutet in Stockholm.

Marc Ladanyi, MD

Memorial Sloan-Kettering Cancer Center
e-mail | website | publications

Marc Ladanyi received his MD from McGill University in Montreal and is presently Attending Pathologist in Molecular Diagnostics Service of the Department of Pathology and a member in the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York. In 2004, as head of the clinical molecular diagnostic laboratories at MSKCC, Ladanyi established rapid and sensitive EGFR mutation detection assays that allowed early implementation of tumor mutation testing, making the discovery of EGFR mutations in lung cancer immediately relevant to the routine care of lung cancer patients. Beyond EGFR mutation testing, Ladanyi has also been a leader in recent efforts to introduce into routine practice even broader large-scale screening of lung cancer tumor specimens for additional mutations that can be targets for new drugs. His research laboratory is focused on the genomics and molecular pathogenesis of sarcomas and thoracic malignancies, including lung adenocarcinomas and mesothelioma. Ladanyi has received the Young Investigator Award from the U.S. and Canadian Academy of Pathology (2005) and was awarded the Nina Axelrod Lectureship by the Connective Tissue Oncology Society (2007) and the Caine Halter Hope Now Award from Uniting Against Lung Cancer (2009). In 2010 he was also appointed to the William Ruane Chair in Molecular Oncology at MSKCC. He has authored or coauthored over 200 primary research papers and over 40 reviews and commentaries.


Abbas Abdollahi, PhD

Abbas Abdollahi studied cancer genetics at the University of Pennsylvania School of Medicine and Fox Chase Cancer Center, where he discovered and characterized novel genes. He also held faculty positions at Drexel University and California State University in the areas of biochemistry and nutrition. He has worked as Scientific Review Officer at the Health Group Division of SRA International, Inc. and as Contributing Editor for BioTechniques. Abbas Abdollahi holds a PhD in Environmental Toxicology from Drexel University.

Sponsors

Presented by

  • American Chemical Society, New York Chapter
  • The New York Academy of Sciences

Grant Support

Supported by an educational grant from Genentech, Inc. and Gilead, Inc.

This activity is supported by an educational donation provided by Amgen.

This activity is supported in part by New England Biolabs.

Academy Friends

Bristol-Myers Squibb