Imatinib-resistant KIT mutants

Stable Identifier
R-HSA-9669917
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Imatinib-resistant KIT mutants
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Imatinib is approved for treatment of cancers carrying primary mutations in the KIT receptor. Imatinib binds and inhibits the inactive state of the receptor, including the conformation promoted by exon 11 mutations that relieve the auto-inhibition of the WT protein. Resistance to imatinib arises due to the polyclonal expansion of subpopulations bearing secondary KIT mutations in the ATP binding pocket or the activation loop of the protein (Serrano et al, 2019; reviewed in Roskoski, 2018; Klug et al, 2018; Corless et al, 2011).
Literature References
PubMed ID Title Journal Year
22089421 Gastrointestinal stromal tumours: origin and molecular oncology

Corless, CL, Barnett, CM, Heinrich, MC

Nat. Rev. Cancer 2011
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

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

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

Klug, LR, Kent, JD, Heinrich, MC

Pharmacol. Ther. 2018
Participants
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Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
Mondo
Authored
Rothfels, K  (2020-04-01)
Reviewed
Serrano, C  (2020-03-13)
García-Valverde, A  (2020-03-13)
Pilco-Janeta, D  (2020-03-13)
Created
Rothfels, K  (2019-12-03)
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