Regorafenib-resistant KIT mutants do not bind regorafenib

Stable Identifier
Reaction [transition]
Homo sapiens
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Regorafenib is used as a secondary therapeutic in cases of imatinib-resistant cancers with KIT mutations. Its effectiveness depends on the position of the secondary mutation. Regorafenib is effective in imatinib-resistant tumors carrying secondary mutations in exon 14 (gatekeeper) and most secondary mutations encoded by exons 17 and 18 (activation loop) (Yeh et al, 2017; Miyake et al, 2018; Serrano et al, 2019a,b; reviewed in Roskoski, 2018; Klug et al, 2018).
Literature References
PubMed ID Title Journal Year
28487491 A phase II trial of regorafenib in patients with metastatic and/or a unresectable gastrointestinal stromal tumor harboring secondary mutations of exon 17

Tzen, CY, Chen, MH, Chen, YY, Yang, CY, Yen, CC, Yeh, CN, Chen, JS, Chen, LT

Oncotarget 2017
29334307 Regorafenib regresses an imatinib-resistant recurrent gastrointestinal stromal tumor (GIST) with a mutation in exons 11 and 17 of c-kit in a patient-derived orthotopic xenograft (PDOX) nude mouse model

Miyake, K, Momiyama, M, Eilber, FC, Murakami, T, Russell, T, Miyake, M, Chishima, T, Li, Y, Singh, A, Matsuyama, R, Zhang, Z, Igarashi, K, Elliott, I, Hoffman, RM, Kiyuna, T, Kawaguchi, K, Nelson, SD, Hiroshima, Y, Endo, I

Cell Cycle 2018
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
12181401 Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors

Joensuu, H, Silberman, SL, Capdeville, R, Peng, B, Heinrich, MC, Singer, S, Roberts, PJ, Blanke, CD, von Mehren, M, Eisenberg, B, Fletcher, JA, Demetri, GD, Kiese, B, Corless, C, Silverman, SG, Fletcher, CD, Druker, BJ, Janicek, M, Dimitrijevic, S, Tuveson, DA, Van den Abbeele, AD

N. Engl. J. Med. 2002
31471313 Phase I Study of Rapid Alternation of Sunitinib and Regorafenib for the Treatment of Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors

Morgan, JA, Phallen, J, Paweletz, CP, Kuang, Y, George, S, Leal, A, Barysauskas, CM, Serrano, C, Triplett, O, Fletcher, JA, Wagner, AJ, Mariño-Enríquez, A, Demetri, GD, Velculescu, VE

Clin. Cancer Res. 2019
Normal reaction
Functional status

Loss of function of regorafenib-resistant KIT mutants [plasma membrane]

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