Format:
Online-Ressource (X, 234 p. 30 illus., 21 illus. in color, digital)
ISBN:
9783642282966
,
9781283865258
Series Statement:
Current Topics in Microbiology and Immunology 355
Content:
Cancer drug development is currently undergoing a profound shift. Drugs targeting fundamental cellular processes such DNA-replication and microtubule function, often referred to as “chemotherapy” and still the backbone of most cancer treatment regimens, are increasingly being complemented by or replaced with kinase inhibitors. This new class of drugs targets enzymes which provide growth and survival signals to cancer cells by transferring phosphate groups from Adenosine-5'-triphosphate (ATP) to other proteins, lipids, nucleotides, and carbohydrates. This book summarizes the current state of kinase inhibitor therapy for cancer. Successful drug development relies on the expertise and dedication of many experts. To reflect this team approach to finding new kinase inhibitors and defining their optimal use for cancer treatment, the editors invited experts in academia and pharmaceutical industry to share their insights into various aspects of this process, ranging from the first chemical screens, to preclinical testing and disease-focused clinical drug development. The editors hope these lessons will be instructive for the novice as well as the expert.
Note:
Description based upon print version of record
,
Setting up a Kinase Discovery and Development Project
,
Therapeutic Kinase Inhibitors; Preface; Contents; Contributors; Part I Fundamentals; 159 Setting up a Kinase Discovery and Development Project; Abstract; 1…Introduction; 2…Choosing the Drug Target; 3…Biochemical Assays for Screening and Counter Screening; 4…Lead Optimization Using Crystallography and Cellular Assays; 5…Improving Pharmaceutical Properties; 6…Efficacy Studies in Mice; 7…Toxicology and Safety Studies; 8…Future Perspectives; References; 160 Drug Efficacy Testing in Mice; Abstract; 1…Introduction; 2…Classical Preclinical Testing in Xenograft Models
,
3…Harnessing Genetically Engineered Murine Models for Drug Efficacy Testing4…Comparing the Track Record of Xenograft and GEM Models; 5…Refining Kinase Inhibitor Therapy in GEMMs; 6…''Credentialing'' GEMMs as Genetically Faithful Models; 7…Logistic Considerations in Developing a ''Mouse Clinic''; 8…Future Perspectives; Acknowledgments; References; Part II Kinase Targets and Disease; 161 Gastrointestinal Stromal Tumors; Abstract; 1…Introduction; 2…KIT Activation as Dominant Pathogenetic Mechanism; 3…GIST with Wild-Type KIT; 4…Treatment of GIST with Imatinib
,
4.1 Imatinib Monotherapy for Advanced GIST4.2 Imatinib Plus Surgery for Advanced GIST; 4.3 Adjuvant Imatinib Therapy After Resection of a Primary GIST; 4.4 Evaluation of Tumor Response to Imatinib; 5…Acquired Imatinib Resistance; 6…Overcoming Imatinib Resistance; 7…Future Perspectives; References; 171 EGFR Mutant Lung Cancer; Abstract; 1…Introduction; 2…First Generation EGFR Kinase Inhibitors; 3…EGFR Kinase Domain Mutations; 4…Primary or ''Upfront'' Resistance to EGFR TKIs; 5…Acquired Resistance to EGFR TKIs; 6…New Approaches to Target EGFR Mutant Lung Cancer; 6.1 Irreversible EGFR Inhibitors
,
6.2 Reversible EGFR Inhibitors with Additional Kinase Targets6.3 Combinations of Targeted Therapy; 6.4 HSP90 Inhibitors; 7…A Uniform Clinical Definition of ''Acquired Resistance'' in NSCLC; 8…Future Perspectives; Acknowledgments; References; 162 Targeting Oncogenic BRAF in Human Cancer; Abstract; 1…Introduction; 2…Somatic BRAF Mutations in Human Tumors; 3…Disabling Physiologic Feedback as a Requirement for RAS-MAPK Activation; 4…MEK Kinase Inhibitors; 5…RAF Kinase Inhibitors; 6…Future Perspective; References; 163 Beyond BRAF in Melanoma; Abstract; 1…Introduction; 2…Melanoma Pathogenesis
,
3…KIT Mutations4…Mutations in G-Protein-Coupled Receptors; 5…Mutations in RAS and RAF Family Members; 6…Mutations at the G1-Checkpoint; 7…The EGF Receptor Family; 8…The PI(3)K-MTOR Pathway in Melanoma; 9…Other Growth Factor Receptor Pathways; 9.1 MET; 9.2 Fibroblast Growth Factor Receptor Family; 10…Future Perspectives; References; 170 JAK-Mutant Myeloproliferative Neoplasms; Abstract; 1…Introduction; 2…Myeloproliferative Neoplasms; 3…Discovery of JAK2V617F Mutations; 4…JAK2V617F-Negative MPN; 5…Additional Somatic Mutations in MPN; 6…Evidence for Germline Mutations in MPN
,
7…Role of JAK-STAT Signaling in Other Malignancies
,
Drug Efficacy Testing in Mice
,
Gastrointestinal Stromal Tumors
,
EGFR Mutant Lung Cancer
,
Targeting Oncogenic BRAF in Human Cancer
,
Beyond BRAF in Melanoma
,
JAK-Mutant Myeloproliferative Neoplasms
,
Will Kinase Inhibitors Make it as Glioblastoma Drugs?
,
Predictive Genomic Biomarkers
,
Epigenetic Biomarkers
,
Adjuvant Trials of Targeted Agents: The Newest Battleground in the War on Cancer
Additional Edition:
ISBN 9783642282959
Additional Edition:
Buchausg. u.d.T. Therapeutic kinase inhibitors Berlin : Springer, 2012 ISBN 9783642282959
Additional Edition:
ISBN 3642282954
Language:
English
Subjects:
Biology
Keywords:
Krebs
;
Proteinkinasen
;
Enzyminhibitor
;
Kinasen
;
Inhibitor
;
Chemotherapie
;
Aufsatzsammlung
DOI:
10.1007/978-3-642-28296-6
URL:
Volltext
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