Oncogene-Directed Therapies

Description

In recent years an entirely new category of anticancer agents has entered the clinic. This class of drugs, the frontrunners of which are Herceptin and Gleevec, are no longer a product of the intuitive and largely empirical explorations that brought about traditional anticancer treatments like chemotherapy. Rather, these new agents have emerged directly from molecular analysis of various cancer-causing genes (oncogenes). In Oncogene-Directed Therapies, prominent investigators and clinicians, several of them pioneers in the field, summarize what is known about oncogenes and oncogenesis-in a balanced blend of fundamental science, basic research, experimental therapeutics, and early clinical experience-and describe how that knowledge can be used to treat the disease. The contributors explain how, why, and under what conditions certain proteins acquire the ability to transform eukaryotic cells, and detail the crucial biological consequences of this oncogenic transformation, particularly for cellular mitogenesis, survival, differentiation, migration, proteolysis, or angiogenic competence. Their articles thoroughly explicate the premises, principles, techniques, and approaches to oncogene targeting in various types of human cancer by using signal transduction inhibitors, immunological targeting methods, and antisense gene therapy. Also included is a review of the results of preclinical and clinical testing of some of today's most advanced therapeutic agents. Unique in perspective and comprehensive in its coverage, Oncogene-Directed Therapies not only integrates for all those engaged in-or simply interested in the cutting-edge of-"the war on cancer" the many remarkable recent achievements in our molecular understanding and treatment of these diseases, but also clarifies what directions future research might optimally take, as well as what significant accomplishments might lie ahead. Front Matter....Pages i-xiii Front Matter....Pages 1-1 Genetic Basis of Cancer Progression....Pages 3-17 The Molecular Basis of Chromosomal Instability in Human Cancer Cells....Pages 19-33 Signal Transduction Networks....Pages 35-46 Oncogenic Receptor Tyrosine Kinases....Pages 47-75 Ras-Mediated Deregulation of Gene Expression and Contribution to Oncogenesis....Pages 77-99 The Interplay Between Tumor Suppressor Genes and Oncogenes in Tumorigenesis....Pages 101-112 Genetic Basis of Altered Responsiveness of Cancer Cells to Their Microenvironment....Pages 113-129 Front Matter....Pages 131-131 Deregulation of Cell Cycle Progression by Oncogenic Transformation....Pages 133-151 Oncogenes as Regulators of Cell Survival....Pages 153-169 Oncogenes and Tumor Angiogenesis....Pages 171-218 Oncogenes as Therapeutic Targets to Prevent Metastasis....Pages 219-228 The Impact of Oncogenes on Tumor Maintenance....Pages 229-243 Primary and Secondary Events in Oncogene-Driven Tumor Development....Pages 245-294 Front Matter....Pages 295-295 Targeting Oncogenes in Hematopoietic Malignancies....Pages 297-311 Clinical Evaluation of Agents Targeting Epidermal Growth Factor Receptor (EGFR) in Cancer....Pages 313-330 Inhibition of the HER-2/neu Oncogene....Pages 331-351 Farnesyltransferase Inhibitors as Anticancer Agents....Pages 353-362 Targeting Oncogenic Signaling Pathways in Human Astrocytomas....Pages 363-382 Targeting Oncogenes in Pediatric Malignancies....Pages 383-408 Inhibiting Signal Transduction as an Approach to Radiosensitizing Tumor Cells....Pages 409-432 Front Matter....Pages 295-295 Oncogenes as Targets for Cancer Vaccines....Pages 433-452 Bcl-2 Antisense Oligonucleotides Therapy for Cancer....Pages 453-468 Back Matter....Pages 469-486