Journal ArticleDOI
Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice.
Nicole M. Agostino,Vernon M. Chinchilli,Christopher J. Lynch,Anita Koszyk-Szewczyk,Rebecca Gingrich,Jeffrey Sivik,Joseph J. Drabick +6 more
TLDR
Inhibition of a tyrosine kinase, be it c-kit, PDGFRβ or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option.Abstract:
Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging pathways. Understanding the role of particular tyrosine kinases in malignancies has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target these enzymes and interfere with downstream signaling. TKIs have proven to be successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and gastrointestinal stromal tumor, and other malignancies. Scattered reports have suggested that these agents appear to affect blood glucose (BG). We retrospectively studied the BG concentrations in diabetic (17) and nondiabetic (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53 mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All these declines in BG were statistically significant. Of note, 47% (8/17) of the patients with diabetes were able to discontinue their medications, including insulin in some patients. Only one diabetic patient developed symptomatic hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the four agents tested, c-kit and PDGFRβ are the common target kinases. Clinicians should keep the potential hypoglycemic effects of these agents in mind; modification of hypoglycemic agents may be required in diabetic patients. These results also suggest that inhibition of a tyrosine kinase, be it c-kit, PDGFRβ or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option.read more
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European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia
J.L. Steegmann,Michele Baccarani,Massimo Breccia,L.F. Casado,Valentín García-Gutiérrez,Andreas Hochhaus,Dong-Kee Kim,Theo-D. Kim,Hanna Jean Khoury,P. le Coutre,Jiří Mayer,Dragana Milojkovic,Kimmo Porkka,Delphine Rea,Giovanni Rosti,Susanne Saussele,Ruediger Hehlmann,Richard E. Clark +17 more
TL;DR: An optimal management of AEs will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life, according to the European LeukemiaNet panel for CML management recommendations.
Journal ArticleDOI
Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes.
Thomas Force,Kyle L. Kolaja +1 more
TL;DR: It is hoped that a thorough understanding of the mechanisms underlying cardiotoxicity will lead to the development of safe, effective drugs and consequently, fewer costly surprises as agents progress through clinical trials.
Journal ArticleDOI
Chronic Myeloid Leukaemia
TL;DR: This Seminar summarises the presentation, pathophysiology, diagnosis and monitoring technology, treatment options, side-effects, and outcomes of chronic myeloid leukaemia, and discusses the possibility of cure-ie, stable undetectable or low level disease in the absence of medication.
Journal ArticleDOI
Saturated Fatty Acids Induce c-Src Clustering within Membrane Subdomains, Leading to JNK Activation
Ryan G. Holzer,EekJoong Park,Ning Li,Helen Tran,Monica Chen,Crystal Choi,Giovanni Solinas,Michael Karin +7 more
TL;DR: It is demonstrated that saturated FA activate JNK and inhibit insulin signaling through c-Src activation, which is more likely to cause insulin resistance and type 2 diabetes than unsaturated FA.
Journal ArticleDOI
Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib
Theo-D. Kim,Delphine Rea,Michaela Schwarz,Peggy Grille,F. E. Nicolini,Giovanni Rosti,Luciano Levato,Francis J. Giles,Hervé Dombret,Tristan Mirault,H Labussière,Ruhdja Lindhorst,Wilhelm Haverkamp,Ivo Buschmann,Bernd Dörken,P. le Coutre +15 more
TL;DR: PAOD is more frequently observed in patients receiving nilotinib as compared with imatinib, and longitudinal non-invasive monitoring and careful assessment of risk factors is warranted.
References
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Discovery and development of sorafenib: a multikinase inhibitor for treating cancer
Scott Wilhelm,Christopher A. Carter,Mark Lynch,Timothy B. Lowinger,Jacques Dumas,Roger A. Smith,Brian Schwartz,Ronit Simantov,Susan Kelley +8 more
TL;DR: The discovery and continuing development of sorafenib is described, the first oral multikinase inhibitor that targets Raf and affects tumour signalling and the tumour vasculature.
Journal ArticleDOI
Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice
Cédric Louvet,Gregory L. Szot,Jiena Lang,Michael R. Lee,Nicolas Martinier,Gideon Bollag,Shirley Zhu,Arthur Weiss,Jeffrey A. Bluestone +8 more
TL;DR: It is strongly suggested that inhibition of PDGFR is critical to reverse diabetes and highlight a crucial role of inflammation in the development of T1D.
Journal ArticleDOI
Imatinib and Regression of Type 2 Diabetes
TL;DR: A nulliparous, 70-year-old woman with long-standing type 2 diabetes mellitus who had regression of the disease during treatment of chronic myeloid leukemia with imatinib, an antineoplastic agent is reported.
Journal ArticleDOI
The biology of Kit in disease and the application of pharmacogenetics.
Cem Akin,Dean D. Metcalfe +1 more
TL;DR: This review will discuss the pathobiology of Kit in human disease, with a particular emphasis on implications for potential targeted treatment strategies in mast cell disease.