TAILIEUCHUNG - Chapter 080. Cancer Cell Biology and Angiogenesis (Part 6)

Imatinib has also demonstrated targeted activity in other diseases, including gastrointestinal stromal tumors (GIST), rare mesenchymal tumors of the GI tract (stomach and small intestine). The pathogenic molecular event for most patients with this disease is mutation of the proto-oncogene c-Kit, leading to the constitutive activation of this receptor tyrosine kinase without the binding of its physiologic ligand, stem cell factor. About 10% of GISTs encode activating mutations of the PDGFRα instead of c-Kit. GISTs are thought to arise from or share a common stem cell with the interstitial cells of Cajal, which give rise to the myenteric plexus. | Chapter 080. Cancer Cell Biology and Angiogenesis Part 6 Imatinib has also demonstrated targeted activity in other diseases including gastrointestinal stromal tumors GIST rare mesenchymal tumors of the GI tract stomach and small intestine . The pathogenic molecular event for most patients with this disease is mutation of the proto-oncogene c-Kit leading to the constitutive activation of this receptor tyrosine kinase without the binding of its physiologic ligand stem cell factor. About 10 of GISTs encode activating mutations of the PDGFRa instead of c-Kit. GISTs are thought to arise from or share a common stem cell with the interstitial cells of Cajal which give rise to the myenteric plexus of the GI tract. Imatinib which inhibits the c-Kit kinase domain has demonstrated significant activity 50 partial responses usually lasting 1-2 years in this chemotherapy-refractory tumor. Resistance to imatinib develops due to secondary mutations in c-Kit and many of these tumors are susceptible to treatment with the multitargeted TK inhibitor sunitinib that has activity against c-Kit as well as the PDGF and vascular endothelial growth factor VEGF receptors. Sunitinib is approved by the . Food and Drug Administration for treatment of patients with imatinib-resistant GIST or who are intolerant of imatinib Table 802 . Interestingly tumors with mutations in exon 11 of c-Kit s juxtamembrane region are particularly sensitive to imatinib whereas those with exon 9 mutations extracellular domain respond better to sunitinib than imatinib. In the future primary therapy for GIST may be determined by the specific molecular defect in c-Kit. Patients with chronic myelomonocytic leukemia CMML a myeloproliferative disorder often harbor a Tel-PDGFR translocation that results in constitutive activation of the PDGFR kinase domain exclusively in the leukemic cells. Imatinib inhibits this kinase and has demonstrated significant activity in this disease. These examples extend the proof of .

• Y học thường thức
• Cancer Cell Biology and Angiogenesis
• bệnh học và điều trị
• bài giảng bệnh học
• tài liệu y khoa
• Harrisons Internal Medicine
• medical books
• pharmacology
• epidemiologic
• Obstetrics
• anatomy
• Preventing Morbidity
• Multidisciplinary Care