Emerging FMS-like tyrosine kinase 3 inhibitors for the treatment of acute myelogenous leukemia
| Autor: | Farhad Ravandi, Hillary Prescott, Hagop M. Kantarjian, Jorge E. Cortes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Myeloid Drug Evaluation Preclinical Pharmacology Article Myelogenous fluids and secretions hemic and lymphatic diseases Medicine Animals Humans Multicenter Studies as Topic Pharmacology (medical) Protein Kinase Inhibitors Randomized Controlled Trials as Topic Clinical Trials as Topic business.industry Cytogenetics hemic and immune systems medicine.disease Leukemia Leukemia Myeloid Acute medicine.anatomical_structure fms-Like Tyrosine Kinase 3 Tyrosine Kinase 3 embryonic structures Fms-Like Tyrosine Kinase 3 Cancer research business FLT3 Inhibitor Tyrosine kinase |
| Popis: | The FMS-like tyrosine kinase 3 (FLT3) is highly expressed in acute leukemias. Mutations involving FLT3 are among the most common molecular abnormalities in acute myelogenous leukemia (AML). Available evidence suggests that these molecular lesions confer a shorter disease-free survival and overall survival in patients with intermediate-risk cytogenetics. Therefore, substantial interest in FLT3 as a therapeutic target has led to the development of several promising inhibitors that target this tyrosine kinase.This review covers the molecular pathways associated with FLT3 activation in patients with AML, the biological rationale for inhibiting FLT3 and recent clinical progress with FLT3 inhibitors for the treatment of AML. Six FLT3 inhibitors undergoing clinical evaluation are discussed. A review of selected published manuscripts on the subject of FLT3 inhibition in AML and a search of the English language manuscripts in PubMed using the index words FLT3 and AML were conducted and articles of interest selected.Mutated forms of FLT3, specifically FLT3-internal tandem duplication, have a significant impact on the prognosis of AML patients, particularly those with a normal karyotype. Inhibiting FLT3 may lead to clinical benefit for patients with AML. Newly developed FLT3 inhibitors have shown encouraging activity as monotherapy and in combination with other therapeutic agents. |
| Databáze: | OpenAIRE |
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