Sunitinib-resistant KIT mutants do not bind sunitinib

Stable Identifier
Reaction [transition]
Homo sapiens
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Sunitinib is an approved therapeutic for the treatment of KIT mutant cancers. Sunitinib is effective against KIT primary mutations and against secondary mutations in the ATP-binding domain encoded by exon 13 and exon 14, but less effective against activation loop mutations encoded by exon 17 and 18, which show resistance to the drug (Nishida et al, 2009; Serrano et al, 2017; Serrano et al, 2019; Gajiwala et al, 2008; Garner et al, 2014; Roskoski, 2018)
Literature References
PubMed ID Title Journal Year
25239608 Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients

Anjum, R, Heinrich, MC, Ketzer, J, Bauer, S, Zhu, M, Zhou, T, Serrano, C, Song, Y, Fletcher, JA, Schrock, A, Ning, Y, Eilers, G, Wardwell, S, Gozgit, JM, Kohlmann, A, Garner, AP, Rivera, VM, Vodala, S, Clackson, T, Wang, F

Clin. Cancer Res. 2014
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
19390946 Sunitinib-resistant gastrointestinal stromal tumors harbor cis-mutations in the activation loop of the KIT gene

Doi, T, Nakajima, K, Nishida, T, Nishitani, A, Takahashi, T, Komatsu, Y, Japanese Study Group on Gist, -, Hirota, S, Shirao, K

Int. J. Clin. Oncol. 2009
29704617 The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
19164557 KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients

Quenzer, T, Emmett, MR, Deshmukh, GD, Lunney, EA, English, JM, Wu, JC, Christensen, J, Molina, D, He, YA, Zhang, Y, Greig, MJ, Demetri, GD, Yu, X, Diehl, W, McTigue, M, Gajiwala, KS, DiNitto, JP, Wells, PA, Jacques, SL, Zou, A, Zhang, HM, Marshall, AG

Proc. Natl. Acad. Sci. U.S.A. 2009
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
Normal reaction
Functional status

Loss of function of sunitinib resistant KIT mutants [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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