A Review on Imatinib: A wonder drug in Oncology

Abstract

Imatinib is one of the first cancer therapies that has shown a potential for a novel approach in cancer treatment. Imatinib represents a therapeutic breakthrough as a targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) specifically BCR-ABL, c-KIT, PDGFRA. It has become the first line drug in management of several cancers. Apart from its remarkable success in CML, it has also shown promising results in the treatment of gastro-intestinal stromal tumors, clonal eosinophilic disorders, philadelphia chromosome positive acute lymphatic leukemia and in steroid-refractory chronic graftversus-host disease because of its anti-PDGFR action. Introduction of Imatinib has radically improved the outcome of patients and has geared up further research into development of designer drugs with molecular targets. Apart from clinical profits of Imatinib in several cancers, it is associated with drug resistance and intolerance. This article gives a comprehensive review of the development, biology, utility, dosing, and limitations of Imatinib in oncology.

The effect of imatinib administered in the prenatal period on testis development in rats

“…4 Only a few (<5) spermatozoa present and no spermatids or spermatozoa present. 5 No spermatozoa, no spermatids but several or many spermatocytes present. 6 No spermatozoa and only a few spermatids (<5-10) present.…”

“…3 It is also used in the treatment of CML and gastrointestinal tumors by targeting c-kit and PDGFR kinases. 4,5 The c-kit ligand stem cell factor (SCF) is involved in events such as chemotaxis, proliferation, differentiation and even survival by activating numerous pathways. 6 Previous studies reported that c-kit is expressed in primordial germ cells and by various cells during germ cell migration and that it can serve as a marker through involvement in cell selection and preservation during migration.…”

“…3 It is also used in the treatment of CML and gastrointestinal tumors by targeting c-kit and PDGFR kinases. 4,5…”

SAR Probing of KX2-391 Provided Analogues With Juxtaposed Activity Profile Against Major Oncogenic Kinases

“…For instance, imatinib, the first FDA approved tyrosine kinase inhibitor (YKI), has been recognized as an inhibitor of BCR–ABL, c-KIT and PDGFR. Because of its multiple activities, imatinib has found use beyond the original designation for the treatment of chronic myeloid leukemia (CML) ( 8 ). Thus, polypharmacologic YKIs have become a common approach in this arena as researchers have become less concerned over the lack of kinase selectivity ( 9 , 10 ).…”