Extensive research into the molecular mechanisms of cancer disease has heralded a new age of targeted therapy. In malignant cells, key proteins that are crucial to tumor growth and survival are now being targeted directly with rationally designed inhibitors. Apart from monoclonal antibodies, small molecule therapeutics such as oncogenic protein kinase inhibitors are attracting a vast amount of investigational attention. This textbook, written by acknowledged experts, provides a broad overview of the small molecules currently used for the treatment of malignant diseases and discusses interesting novel compounds that are in the process of clinical development to combat cancer.

1;Recent Results in Cancer Research;1 1.1;Protein Kinase Inhibitors;15 1.1.1;Imatinib Mesylate;16 1.1.1.1;Introduction;16 1.1.1.2;Chemical Structure;18 1.1.1.3;Clinical Pharmacology;19 1.1.1.4;Drug Targets;19 1.1.1.5;Preclinical Studies;19 1.1.1.6;Clinical Data in CML;21 1.1.1.6.1;Phase I Trials;21 1.1.1.6.2;Phase II Studies;21 1.1.1.6.3;Phase III Study (IRIS-Trial);22 1.1.1.6.4;Side Effects/Toxicity;23 1.1.1.7;Disease Progression and Imatinib Resistance;24 1.1.1.8;Treatment Recommendations for the Use of Imatinib in Chronic Phase CML;27 1.1.1.9;Imatinib in Combination with Other Drugs;28 1.1.1.10;Imatinib - Other Targets;28 1.1.1.11;Conclusion and Future Perspectives;29 1.1.2;References;30 1.1.3;Erlotinib;34 1.1.3.1;Introduction;34 1.1.3.2;Mechanism of Action;35 1.1.3.3;Non-Small Cell Lung Cancer;35 1.1.3.4;Pancreatic Adenocarcinoma;37 1.1.3.5;Hepatocellular Carcinoma;40 1.1.3.6;Other Tumour Entities;41 1.1.4;References;41 1.1.5;Axitinib (AG-013736);45 1.1.5.1;Introduction;45 1.1.5.2;Structure of Molecule;46 1.1.5.3;Preclinical Data;46 1.1.5.3.1;Bioavailability in Humans;48 1.1.5.4;Phase II Studies;48 1.1.5.4.1;3.4.1Axitinib in Renal Cell Carcinoma;48 1.1.5.4.2;Axitinib in Pancreatic Cancer;49 1.1.5.4.3;Axitinib in Metastatic Breast Cancer;50 1.1.5.4.4;Axitinib in Thyroid Cancer;50 1.1.5.4.5;Axitinib in Other Solid Tumors;51 1.1.5.5;Phase III Studies;51 1.1.5.6;Toxicity;52 1.1.5.7;Drug Interactions;53 1.1.5.8;Future;54 1.1.6;References;54 1.1.7;Lapatinib;57 1.1.7.1;4.1.Introduction;57 1.1.7.1.1;4.1.1.The Epidermal Growth Factor Receptor Family of Tyrosine Kinases;57 1.1.7.1.2;4.1.2.Human Epidermal Growth Factor Receptors and Breast Cancer;59 1.1.7.2;4.2.Structure and Mechanism of Action;59 1.1.7.3;4.3.Clinical Data;61 1.1.7.3.1;4.3.1.Pharmacology;61 1.1.7.3.2;4.3.2.Results from Clinical Trials;61 1.1.7.3.2.1;4.3.2.1.Efficacy;61 1.1.7.3.2.2;4.3.2.2.Tolerability;66 1.1.7.4;4.4.Conclusion and Future Perspectives;66 1.1.8;References;67 1.1.9;Sorafenib;72 1.1.9.1;5.1.Introduction;72 1.1.9.2;5.2.Structure and Mechanism of Action;73 1.1.9.3;5.3.Clinical Data;75 1.1.9.3.1;5.3.1.Phase I;75 1.1.9.3.2;5.3.2.Sorafenib in the Treatment of Renal Cell Cancer (RCC);75 1.1.9.3.3;5.3.3.Sorafenib in the Treatment of Lung Cancer;77 1.1.9.3.4;5.3.4.Sorafenib in the Treatment of Hepatocellular Cancer (HCC);77 1.1.9.3.5;5.3.5.Sorafenib in the Treatment of Breast Cancer;77 1.1.9.3.6;5.3.6.Sorafenib in the Treatment of Malignant Melanoma;77 1.1.9.3.7;5.3.7.Sorafenib in the Treatment of Prostate Cancer;78 1.1.9.3.8;5.3.8.Sorafenib in the Treatment of Head and Neck Cancer;78 1.1.9.3.9;5.3.9.Sorafenib in the Treatment of Ovarian Cancer;78 1.1.9.3.10;5.3.10.Sorafenib in the Treatment of Brain Tumors;78 1.1.9.3.11;5.3.11.Sorafenib in the Treatment of Thyroid Cancer;78 1.1.9.3.12;5.3.12.Sorafenib in the Treatment of Hematologic Diseases;78 1.1.9.4;5.4.Conclusion and Future Perspectives;79 1.1.10;References;79 1.1.11;Sunitinib;82 1.1.11.1;Introduction;82 1.1.11.2;Sunitinib;82 1.1.11.3;Renal Cell Carcinoma;83 1.1.11.3.1;6.3.1Targets for Renal Cell Carcinoma;83 1.1.11.3.2;Phase II/III Studies in Metastatic RCC;85 1.1.11.4;Gastrointestinal Stromal Tumors;86 1.1.11.4.1;Targets for Gastrointestinal Stromal Tumors;86 1.1.11.4.2;GIST Clinical Trials;86 1.1.11.4.3;Side Effects;87 1.1.11.4.4;Drug Interactions;89 1.1.11.4.5;Activity in Other Tumor Sites and Ongoing Research;89 1.1.11.5;Conclusion;90 1.1.12;References;90 1.1.13;Dasatinib;94 1.1.13.1;Introduction;94 1.1.13.2;Structure and Mechanism of Action;96 1.1.13.2.1;Inhibition of ABL;97 1.1.13.2.2;Inhibition of SRC;98 1.1.13.2.3;Inhibition of c-KIT;98 1.1.13.2.4;Inhibition of Platelet-Derived Growth Factor Receptor (PDGFR)-.a. and .b. Tyrosine Kinases;99 1.1.13.2.5;Inhibition of Ephrin Receptor Tyrosine Kinases;99 1.1.13.2.6;Additional Effects;99 1.1.13.3;Clinical Data;99 1.1.13.3.1;Pharmacokinetic Profile;99 1.1.13.3.2;Clinical Studies with Dasatinib in CML and Other Diseases;100 1.1.13.3.3;CML and Ph.+. ALL - O