Novel Anticancer Drug Protocols

ISBN-13: 9781489938398 / Angielski / Miękka / 2013 / 355 str.

John K. Buolamwini; Alex A. Adjei

Opis

We are in an exciting era in the war against cancer, with real prospects for novel anticancer drugs that are cancer cell-specific without the toxicities that have been the hallmark of conventional cytotoxic cancer chemotherapy. Advances in cancer cell biology fueled by the molecular biology revolution have resulted in the uncovering of many novel potential molecular targets for cancer therapy. New anticancer drug discovery and development is now largely focused on exploiting these new molecular targets, which encompass oncogenes, tumor s- pressor genes, and their gene products, as well as targets involved in tumor angiogenesis, metastasis, survival, and longevity mechanisms. Exploitation of some of these targets has already yielded fruits and introduced new paradigms of molecularly targeted cancer therapy into the clinic, namely, protein kinase in- bition by antibodies or small molecules, exemplified by Herceptin(R) (trastuzumab), a humanized antibody targeted against the HER-2 growth factor receptor tyrosine kinase for the treatment of metastatic breast cancer; and Gleevec, a small molecule bcr-abl kinase inhibitor for the treatment of chronic myel- enous leukemia.

Spis treści

Part I. Introduction Overview of Novel Anticancer Drug Targets John K. Buolamwini and Haregewein Assefa Part II. Kinase Inhibitor Discovery Protocols Biomarker Assays for Phosphorylated MAP Kinase: Their Utility for Measurement of MEK Inhibition Judith S. Sebolt-Leopold, Keri Van Becelaere, Kenneth Hook, and Roman Herrera Assays for Cyclin-Dependent Kinase Inhibitors Adrian M. Senderowicz and Tyler Lahusen Identifying Inhibitors of ATM and ATR Kinase Activities Jann N. Sarkaria Part III. Angiogenesis and Metastasis Protocols The Rat Aortic Ring Assay for In Vitro Study of Angiogenesis Ronald S. Go and Whyte G. Owen Real Time In Vivo Quantitation of Tumor Angiogenesis Gregory I. Frost and Per Borgström Use of Tumor-Activated Hepatic Stellate Cell as a Target for the Preclinical Testing of Anti-Angiogenic Drugs Against Hepatic Tumor Development Elvira Olaso and Fernando Vidal-Vanaclocha Cell Motility, Adhesion, Homing, and Migration Assays in the Studies of Tyrosine Kinases Martin Sattler, Elizabeth Quackenbush, and Ravi Salgia Inflammatory Response of Tumor-Activated Hepatic Sinusoidal Endothelium as a Target for the Screening of Metastasis Chemopreventive Drugs Lorea Mendoza and Fernando Vidal-Vanaclocha Binding Assay for Selectins Jianing Zhang and Michiko N. Fukuda Determination of Peak Serum Levels and Immune Response to the Humanized Anti-Ganglioside Antibody-Interleukin-2 Immunocytokine Jacquelyn A. Hank, Jean E. Surfus, Jacek Gan, Amy Ostendorf, Stephen D. Gillies, and Paul M. Sondel Part IV. Immunohistochemical Assays in the Clinical Setting Immunohistochemical Determination of EGFR-Tyrosine Kinase Inhibition in Clinical Samples Shazli N. Malik, Roble G. Bedolla, Manuel Hidalgo, Michael G. Brattain, and Jeffrey I.Kreisberg Immunohistochemical Assays of Farnesyltransferase Inhibition in Patient Samples Alex A. Adjei Part V. Protein Chaperoning/Degradation Protocols Assays for HSP90 and Inhibitors Wynne Aherne, Alison Maloney, Chris Prodromou, Martin G. Rowlands, Anthea Hardcastle, Katherine Boxall, Paul Clarke, Michael I. Walton, Laurence Pearl, and Paul Workman Assays for Proteasome Inhibition Peter J. Elliott, Teresa A. Soucy, Christine S. Pien, Julian Adams, and Eric S. Lightcap Part VI. Protein-Protein and Protein-DNA Interactions The Mammalian Two-Hybrid Assay for Detection of Coactivator-Nuclear Receptor Interactions Curtis M. Tyree and Kay Klausing Preparation of DNA-Protein Complexes Suitable for Spectroscopic Analysis Nouri Neamati, Manisha Murthy, and Yun-Xing Wang Part VII. Antisense Antisense Oligonucleotide Inhibitors of MDM2 Oncogene Expression Ruiwen Zhang and Hui Wang Part VIII. Genomics Pharmacogenetic Analysis of Clinically Relevant Genetic Polymorphisms Christine M. Rose, Sharon Marsh, Margaret-Mary Ameyaw, and Howard L. McLeod Gene Expression Microarrays Christopher P. Kolbert, William R. Taylor, Kelly L. Krajnik, and Dennis J. O'Kane Methods for Isolation and Genetic Analysis of Circulating Tumor DNA in Patient Plasma Tomoya Kawaguchi, Will S. Holland, and Paul H. Gumerlock Part IX. Cell Lifespan/Longevity The Use of Early Sea Urchin Embryos in Anticancer Drug Testing David Nishioka, Vanessa Marcell, Meghan Cunningham, Merium Khan, Daniel D. Von Hoff, and Elzbieta Izbicka Part X. In Vivo Imaging PET Screening of Anticancer Drugs: A Faster Route to Drug/Target Evaluations In Vivo Anna Fredriksson and Sharon Stone-Elander Part XI. Miscellaneous Protocols Assays for In Vitro and In Vivo Synergy

Blurb

With many potential molecular targets of anticancer agents already identified and many more yet to be discovered, the great challenges are now to successfully validate them, to devise relevant assays, and to translate the results into effective medicines for cancer patients. In Novel Anticancer Drug Protocols, expert basic researchers and clinicians from both industry and academia not only survey the whole arena of novel antitumor drug targets, but also present a wide-ranging selection of the key techniques currently being applied throughout anticancer drug discovery and development. Described in step-by-step detail to ensure successful results, these methods are employed in experiments involving such central topics as immunotherapy, angiogenesis, cancer metastasis, the cell cycle, signal transduction inhibitors, apoptosis, antibodies, antisense molecules, microarray gene expression analysis, flow cytometry, and PET imaging for cancer target validation. There are also proven methods for the preclinical identification of drug targets and for target validation during the clinical trials of novel agents. Each method provides background information, easy-to-follow instructions, notes on avoiding pitfalls, and alternative procedures.
Eminently practical and user-friendly, Novel Anticancer Drug Protocols offers all researchers involved in cancer drug development a blend of the critical preclinical and clinical assays needed for the target validation and discovery of novel agents today.