Principles of Chemotherapy and Pharmacology

C K Donawho, A R Shoemaker, and J P Palma, Abbott Laboratories, Abbott Park, IL, USA © 2007 Elsevier Ltd. All Rights Reserved.

7.02.1 Introduction 33

7.02.2 Pharmacology 34

7.02.2.1 Pharmacokinetics: The In Vivo Movement of Drugs 34

7.02.2.2 Pharmacodynamics: The Mechanisms of Drug Action 34

7.02.3 Evaluation of New Drugs or Agents 34

7.02.3.1 Assay Development (High-Throughput) or In Vitro Cell Panels 34

7.02.4 Preclinical Tumor Models in Cancer Drug Discovery 34

7.02.4.1 Common/Classical Preclinical In Vivo Approaches 35

7.02.4.1.1 Subcutaneous or flank tumor models 35

7.02.4.1.2 Liquid/hematologic tumor models 36

7.02.4.1.3 Orthotopic/metastatic tumor models 36

7.02.4.1.4 Transgenics, knockouts, and in vivo gene targeting 37

7.02.4.1.5 Predictive value of murine in vivo models 37

7.02.5 Analysis of Cytotoxic Agents in Xenograft Models 43

7.02.6 Drug Resistance and its Clinical Circumvention 44

7.02.7 Toxicology by Organ Systems 44

7.02.8 Biological Markers and Clinical Development 44

7.02.8.1 Types of Biomarkers 44

7.02.9 Tools for Biomarker Discovery 49

7.02.9.1 Genomics 49

7.02.9.2 Proteomics and Metabolomics 49

7.02.10 Challenges in Biomarker Development 49 References 50

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