KIT mutants bind TKIs

Stable Identifier
Homo sapiens
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Aberrant signaling by activated forms of KIT can be inhibited by tyrosine kinase inhibitors. Primary mutations in KIT are frequently found in exon 11, encoding the juxtamembrane domain responsible for autoinhibition of the kinase. These mutations are generally sensitive to tyrosine kinase inhibitors such as imatinib. Accumulation of secondary mutations in the ATP-binding pocket and the activation loop of the kinase domain contributes to resistance to first line tyrosine kinase inhibitors. KIT receptors with in these regions are sensitive to a panel of additional tyrosine kinase inhibitors such as sunitinib and regorafenib (Serrano et al, 2019; reviewed in Roskoski, 2018; Klug et al, 2018; Serrano et al, 2017).

Literature References
PubMed ID Title Journal Year
28478525 Novel Insights into the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors

Morales-Barrera, R, Carles, J, Suárez, C, García-Valverde, A, Olivares, D, Valverde, C, George, S, Serrano, C

Target Oncol 2017
29704617 The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
30792533 Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours

Heinrich, MC, Ketzer, J, Bauer, S, Zhu, M, Presnell, A, Raut, CP, George, S, Mannan, AM, Serrano, C, Yu, C, Sicinska, E, Tao, DL, Rubin, BP, Fletcher, JA, Mariño-Enríquez, A, Demetri, GD, Eilers, G, Czaplinski, JT, McKinley, A

Br. J. Cancer 2019
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Heinrich, MC, Kent, JD, Klug, LR

Pharmacol. Ther. 2018
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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