Oncogenomics Handbook

An integrated overview of cancer drug discovery and development from the bench to the clinic, showing with broad strokes and representative examples the drug development process as a network of linked components leading from the discovered target to the ultimate therapeutic product. Following a systems biology approach, the authors explain genomic databases and how to discover oncological targets from them, how then to advance from the gene and transcript to the level of protein biochemistry, how next to move from the chemical realm to that of the living cell and, ultimately, pursue animal modeling and clinical development. Emerging cancer therapeutics including Ritux an, Erbitux, Gleevec Herceptin, Avastin, ABX-EGF, Velcade, Kepivance, Iressa, Tarceva, and Zevalin are addressed. Highlights include cancer genomics, pharmacogenomics, transcriptomics, gene expression analysis, proteomic and enzymatic cancer profiling technologies, and cellular and animal approaches to cancer target validation.

Part I. Genomics, Cancer Targets, Transcriptomics, and Gene Expression Analysis Genomic Resources for Cancer Biologists Xuefeng Bruce Ling, Gene Cutler, and Timothy Hoey Cancer Drug Target Identification by SAGE, LongSAGE, and Digital Karyotyping Heiko Hermeking Identification of Novel Cancer Target Antigens Utilizing EST and Genome Sequence Databases Tapan K. Bera, Kristi A. Egland, B. K. Lee, and Ira Pastan Tree-Based Cancer Classification and Diagnosis Using Gene Expression Data Heping Zhang From FISH to Proteomics: A Molecular Brush to Define Antitumor Drug Action Balanehru Subramanian, Alexander Nakeff, and Frederick Valeriote Gene Program Signatures for Papillomavirus E2-Mediated Senescence in Cervical Cancer Cells: Finding the Points of No Return Sarah S. Williams, Bruce J. Aronow, and Susanne I. Wells Part II. Advances in Proteomic and Enzymatic Cancer-Profiling Technologies Mass-Spectrometry-Based Proteomics for Cancer Biology Chen Xu and John R. Yates III Chemical Proteomics in Drug Development Douglas A. Jeffery, Amos Baruch, and Matthew Bogyo Proteomics-Based Anticancer Drug Discovery K. K. Jain Cancer Metabolic Phenotype: Exploiting the Cancer Metabolome in Drug Discovery John R. Griffiths and Marion Stubbs Focusing Target Discovery and Validation Through Proteogenomics and Molecular Imaging Lucy A. Carver and Jan E. Schnitzer Part III. Cancer Target Validation: Cellular Approaches RNA Interference: RNAid for Future Therapeutics? Mustapha Diallo, Katja Schmitz, and Ute Schepers Image-Based Assays of Cellular Phenotype for Drug Target Discovery and Validation Kris F. Sachsenmeier and Jonathan A. Terrett Targeting Inducible Chemotherapy Resistance Mechanisms in Colon Cancer David Ljungman and James C. Cusack, Jr. Targeting Apoptosis Pathways for Cancer Therapy Bharvin K. R. Patel Part IV. Cancer Target Validation: Animal Approaches Genetically Engineered Mouse Models of Human Cancer for Drug Discovery and Development Rónán C. O'Hagan, Min Wu, William M. Rideout III, Yinghui Zhou, and Joerg Heyer Unraveling the Complexity of Oncogenesis Through In Vivo Optical Imaging Pamela Reilly Contag Innovative Strategies for Improving Engineered Mouse Models of Human Cancer for Preclinical Development Jeffrey J. Martino and Suzie Chen Use of Adenovirus-Mediated Gene Transfer to Facilitate Biological Annotation of Novel Genes Jeff L. Ellsworth, Andrew Feldhaus, and Steven D. Hughes Cancer Biology and Transgenic Technology in the Mouse: Bridging the Functional Gap Cindy E. McKinney and Cooduvalli S. Shashikant Homology-Based Genomic Mining of Growth Factors Implicated in Neoplasia and Nephritides: PDGF-D Gary C. Starling, William J. LaRochelle, and Gulshan Ara Part V. Cancer Prognostics, Diagnostics, and Biomarkers Cancer Pharmacogenomics: Predicting Drug Response in the Genomic Era Brian Z. Ring and Huijun Z. Ring Diagnosis and Treatment of Malignancies Using Gene Expression Profiling Jimmy C. Sung, Alice Y. Lee, and Timothy J. Yeatman Implications of Epigenetics for Early Cancer Diagnosis and Prevention Mukesh Verma and Sudhir Srivastava Novel Molecular and Genetic Prognostic Biomarkers in Prostate Cancer Arnab Chakravarti and Gary Guotang Zhai PSA in Prostate Cancer Diagnosis Pradip Datta Tumor Targets and Biomarkers in Renal Cell Carcinoma Ivar Bleumer and Peter F. A. Mulders Part VI. Emerging Approaches to Cancer Therapy VI-A. Targeting the Vasculature Tumor Vasculature as a Target for Cancer Therapy Grzegorz