PURPOSE OF REVIEW: The management of acute myeloid leukemia (AML) presents significant challenges, and there remains a need for new therapies with greater efficacy and better tolerability than existing treatments. An improved understanding of the genetic and molecular changes underlying AML can help both to guide treatment strategies and to predict clinical outcomes, thereby enabling more precise decision-making regarding the optimal treatment strategy for individual patients. RECENT FINDINGS: The tyrosine kinase receptor FLT3 plays an important role in the survival and proliferation of blasts, and approximately 25% of patients with AML have mutations in the FLT3 gene. This protein is therefore an obvious therapeutic target in AML. Amongst recently developed tyrosine kinase inhibitors of FLT3, lestaurtinib and midostaurin are two orally bioavailable agents that have shown encouraging activity, both preclinically and in relapsed AML, and are now in phase III clinical trials. These agents are also being tested in combination with conventional chemotherapy. SUMMARY: Oral FLT3 inhibitors offer a hope of improved treatment outcomes for patients with relapsed and newly diagnosed AML.
PURPOSE OF REVIEW: The management of acute myeloid leukemia (AML) presents significant challenges, and there remains a need for new therapies with greater efficacy and better tolerability than existing treatments. An improved understanding of the genetic and molecular changes underlying AML can help both to guide treatment strategies and to predict clinical outcomes, thereby enabling more precise decision-making regarding the optimal treatment strategy for individual patients. RECENT FINDINGS: The tyrosine kinase receptor FLT3 plays an important role in the survival and proliferation of blasts, and approximately 25% of patients with AML have mutations in the FLT3 gene. This protein is therefore an obvious therapeutic target in AML. Amongst recently developed tyrosine kinase inhibitors of FLT3, lestaurtinib and midostaurin are two orally bioavailable agents that have shown encouraging activity, both preclinically and in relapsed AML, and are now in phase III clinical trials. These agents are also being tested in combination with conventional chemotherapy. SUMMARY: Oral FLT3 inhibitors offer a hope of improved treatment outcomes for patients with relapsed and newly diagnosed AML.
Authors: Raymond Kwan; Lu Chen; Koksun Looi; Guo-Zhong Tao; Sujith V Weerasinghe; Natasha T Snider; Mary Anne Conti; Robert S Adelstein; Qing Xie; M Bishr Omary Journal: Hepatology Date: 2015-08-25 Impact factor: 17.425
Authors: Huimin Geng; Sarah Brennan; Thomas A Milne; Wei-Yi Chen; Yushan Li; Christian Hurtz; Soo-Mi Kweon; Lynette Zickl; Seyedmehdi Shojaee; Donna Neuberg; Chuanxin Huang; Debabrata Biswas; Yuan Xin; Janis Racevskis; Rhett P Ketterling; Selina M Luger; Hillard Lazarus; Martin S Tallman; Jacob M Rowe; Mark R Litzow; Monica L Guzman; C David Allis; Robert G Roeder; Markus Müschen; Elisabeth Paietta; Olivier Elemento; Ari M Melnick Journal: Cancer Discov Date: 2012-10-29 Impact factor: 39.397