Molecular Oncology: Causes of Cancer and Targets for Treatment

doi:10.1017/CBO9781139046947

The genomic era has allowed enormous strides in our understanding of the molecular changes that underlie malignant transformation. Mutations have been discovered that are critical drivers of large cross-sections of human cancers. These discoveries have allowed us to find drugs that target these drivers and make important strides in treatment. Genomics and high-throughput technologies have illuminated the complexity of cancer and the facility with which cancers adapt during their natural history. The field is evolving rapidly with new discoveries and new drugs reported monthly. This book is a timely foundation for understanding in context the origins of molecular oncology and its future directions. The content reviews available technologies for the analysis of cancer tissues and genes; summaries of key oncogenic pathways from a molecular perspective; the technologies, pathways and targeted therapies of a wide range of human malignancies; and new pharmacologic therapies that have a common mechanistic target.

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Contents

Frontmatter
pp i-iv
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Dedication
pp v-vi
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Contents
pp vii-x
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List of Contributors
pp xi-xx
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Preface
pp xxi-xxii
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Part 1.1 - Analytical techniques: analysis of DNA
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1 - Cancer genome sequencing
pp 1-9
- By Abizar Lakdawalla, Illumina, Inc., San Diego, CA, USA, Jeffrey Fisher, Illumina, Inc., San Diego, CA, USA, Mostafa Ronaghi, Illumina, Inc., San Diego, CA, USA, Jian-Bing Fan, Illumina, Inc., San Diego, CA, USA
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2 - Genome-wide association studies of cancer predisposition
pp 10-20
- By Zsofia K. Stadler, Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, Sohela Shah, Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, Kenneth Offit, Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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3 - Comparative genomic hybridization
pp 21-27
- By Donna G. Albertson, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA, Daniel Pinkel, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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4 - Chromosome analysis: molecular cytogenetic approaches
pp 28-36
- By Thomas Ried, Section of Cancer Genomics, Genetics Branch, Center for Cancer Research /NCI/NIH, Bethesda, MD, USA
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5 - DNA methylation
pp 37-45
- By Marsha Reyngold, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, Timothy A. Chan, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Part 1.2 - Analytical techniques: analysis of RNA
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6 - The application of high-throughput analyses to cancer diagnosis and prognosis
pp 46-51
- By Edward P. Gelmann, Departments of Medicine and Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA
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7 - Cancer proteomics
pp 52-57
- By Samir Hanash, Fred Hutchinson Cancer Research Center, Seattle,WA, USA, Ayumu Taguchi, Fred Hutchinson Cancer Research Center, Seattle,WA, USA
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8 - Tyrosine kinome profiling: oncogenic mutations and therapeutic targeting in cancer
pp 58-75
- By Paramita Ghosh, Departments of Biochemistry and Molecular Medicine, and Urology, University of California David School of Medicine, Sacramento, and VA Northern Health Care System, Mather, CA, USA, Yun Qiu, Department of Pharmacology and Experimentalherapeutics, University of Maryland School of Medicine, Baltimore, MD, USA, Ling-Yu Wang, Department of Stem Cell Biology and Regenerative Medicine, Kimmel Cancer Center,homas Jeferson University, Philadelphia, PA, USA, Hsing-Jien Kung, Departments of Biochemistry and Molecular Medicine, and Urology, University of California David School of Medicine, Sacramento, CA, USA
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9 - In situ techniques for protein analysis in tumor tissue
pp 76-84
- By Valsamo K. Anagnostou, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA, David L. Rimm, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
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Part 2.1 - Molecular pathways underlying carcinogenesis: signal transduction
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10 - HER
pp 85-109
- By Wolfgang J. Köstler, Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel, Yosef Yarden, Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
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11 - The insulin–insulin-like growth-factor receptor family as a therapeutic target in oncology
pp 110-118
- By Michael Pollak, Department of Oncology, McGill University, Montreal, Quebec, Canada
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12 - TGF-β signaling in stem cells and tumorigenesis
pp 119-134
- By Ying Li, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA, Ruth He, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA, Lopa Mishra, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA
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13 - Platelet-derived growth factor
pp 135-143
- By Arne Östman, Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden, Carl-Henrik Heldin, Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
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14 - FMS-related tyrosine kinase 3
pp 144-161
- By Soheil Meshinchi, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA,USA, Derek L. Stirewalt, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA,USA
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15 - ALK: Anaplastic lymphoma kinase
pp 162-189
- By Karen Pulford, Nuield Division of Clinical Laboratory Sciences, Radclife Department of Medicine, University of Oxford, Oxford, UK
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16 - The FGF signaling axis in prostate tumorigenesis
pp 190-203
- By Fen Wang, Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX,USA, Yongde Luo, Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USA, Wallace L. McKeehan, Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USA
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17 - Hepatocyte growth factor/Met signaling in cancer
pp 204-217
- By Fabiola Cecchi, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda,MD, USA, Young H. Lee, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Donald P. Bottaro, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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18 - PI3K
pp 218-230
- By Kevin D. Courtney, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas, TX, USA, Lewis C. Cantley, Weill Cornell Cancer Center, New York – Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA
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19 - Intra-cellular tyrosine kinase
pp 231-242
- By Rosalyn B. Irby, Penn State Hershey Cancer Institute H046, Penn State University College of Medicine, Hershey, PA, USA, Timothy J. Yeatman, Gibbs Cancer Center and Research Institute, Spartanburg, SC, USA
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20 - WNT signaling in neoplasia
pp 243-257
- By Masaru Katoh, Genetics and Cell Biology Section, National Cancer Center, Tokyo, Japan
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21 - Ras
pp 258-271
- By Adrienne D. Cox, Departments of Radiation Oncology and Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, Molly J. DeCristo, Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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22 - BRAF mutations in human cancer: biologic and therapeutic implications
pp 272-277
- By Moriah H. Nissan, Human Oncology and Pathogenesis Program, and Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, David B. Solit, Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Molecular Oncology

Causes of Cancer and Targets for Treatment

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