دورية أكاديمية
Understanding the molecular-based mechanism of action of the tyrosine kinase inhibitor: sunitinib.
| العنوان: | Understanding the molecular-based mechanism of action of the tyrosine kinase inhibitor: sunitinib. |
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| المؤلفون: | Mena AC; Medical Oncology Department, Universitary Hospital Ramon y Cajal, Madrid, Spain. acarrato@telefonica.net, Pulido EG, Guillén-Ponce C |
| المصدر: | Anti-cancer drugs [Anticancer Drugs] 2010 Jan; Vol. 21 Suppl 1, pp. S3-11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9100823 Publication Model: Print Cited Medium: Internet ISSN: 1473-5741 (Electronic) Linking ISSN: 09594973 NLM ISO Abbreviation: Anticancer Drugs Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Lippincott Williams & Wilkins Original Publication: Oxford, UK : Rapid Communications of Oxford, [1990- |
| مواضيع طبية MeSH: | Angiogenesis Inhibitors/*pharmacology , Indoles/*pharmacology , Neovascularization, Pathologic/*drug therapy , Protein Kinase Inhibitors/*pharmacology , Protein-Tyrosine Kinases/*antagonists & inhibitors , Pyrroles/*pharmacology, Angiogenesis Inhibitors/therapeutic use ; Breast Neoplasms/blood supply ; Breast Neoplasms/drug therapy ; Carcinoma, Renal Cell/blood supply ; Carcinoma, Renal Cell/drug therapy ; Colonic Neoplasms/blood supply ; Colonic Neoplasms/drug therapy ; Drug Resistance, Neoplasm ; Female ; Gastrointestinal Stromal Tumors/blood supply ; Gastrointestinal Stromal Tumors/drug therapy ; Humans ; Indoles/therapeutic use ; Lung Neoplasms/blood supply ; Lung Neoplasms/drug therapy ; Neovascularization, Pathologic/enzymology ; Protein Kinase Inhibitors/therapeutic use ; Pyrroles/therapeutic use ; Sunitinib |
| مستخلص: | Sunitinib is an orally available small-molecule multikinase inhibitor. This agent potently inhibits the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit in addition to other kinases in biochemical and cell-based assays. In several relevant preclinical cancer models, sunitinib exerts significant antiangiogenesis and antitumor effects. In phase I studies, using intermittent dosing schedules, oral administration of doses up to 50 mg/day were reasonably well tolerated and resulted in plasma concentrations in the range of targeted levels needed for sustained kinase inhibition. Biomarker and functional imaging studies showed modulation of circulating markers of angiogenesis as well as a reduction in tumor metabolism. Sunitinib showed clinical activity in patients with renal cell cancer and in patients with imatinib-resistant gastrointestinal stromal tumors. Definitive randomized clinical trials showed significant clinical activity in these two indications leading to regulatory approval. In addition, this drug has showed activity in a variety of other tumor types such as breast, colon, and lung cancer and is being explored in combination with standard drugs in these diseases. The observation that biological and functional imaging effects are reduced during drug-free intervals has prompted the evaluation of protracted dosing schedules. A better understanding of mechanisms involved in resistance to sunitinib provides the rationale for combination strategies that hopefully will result in better clinical effect. Ongoing studies will elucidate the overall role of this drug in cancer treatment. |
| Number of References: | 63 |
| المشرفين على المادة: | 0 (Angiogenesis Inhibitors) 0 (Indoles) 0 (Protein Kinase Inhibitors) 0 (Pyrroles) EC 2.7.10.1 (Protein-Tyrosine Kinases) V99T50803M (Sunitinib) |
| تواريخ الأحداث: | Date Created: 20100130 Date Completed: 20100312 Latest Revision: 20181201 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1097/01.cad.0000361534.44052.c5 |
| PMID: | 20110785 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1473-5741 |
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| DOI: | 10.1097/01.cad.0000361534.44052.c5 |