Nilotinib-resistant KIT mutants do not bind nilotinib

Stable Identifier
R-HSA-9669868
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

A number of secondary mutations that arise in mutated KIT receptors confer resistance to nilotinib. This is particularly true for the 'gate-keeper' mutation T760I that increases the affinity of the receptor for ATP, rendering it less susceptible to ATP-competitive inhibitors (Kissova et al, 2016; Serrano et al, 2019; Guo et al, 2007; Roberts et al, 2007; reviewed in Klug et al, 2018; Roskoski, 2018).

Literature References
PubMed ID Title Journal Year
17363509 Resistance to c-KIT kinase inhibitors conferred by V654A mutation

Roberts, KG, Odell, AF, Byrnes, EM, Baleato, RM, Griffith, R, Lyons, AB, Ashman, LK

Mol. Cancer Ther. 2007
17699867 Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor

Guo, T, Agaram, NP, Wong, GC, Hom, G, D'Adamo, D, Maki, RG, Schwartz, GK, Veach, D, Clarkson, BD, Singer, S, DeMatteo, RP, Besmer, P, Antonescu, CR

Clin. Cancer Res. 2007
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
27527414 The human tyrosine kinase Kit and its gatekeeper mutant T670I, show different kinetic properties: Implications for drug design

Kissova, M, Maga, G, Crespan, E

Bioorg. Med. Chem. 2016
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
Cite Us!