Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F

Alice T. Shaw; Luc Friboulet; Ignaty Leshchiner; Justin F. Gainor; Simon Bergqvist; Alexei Brooun; Benjamin J. Burke; Ya Li Deng; Wei Liu; Leila Dardaei; Rosa L. Frias; Kate R. Schultz; Jennifer Logan; Leonard P. James; Tod Smeal; Sergei Timofeevski; Ryohei Katayama; A. John Iafrate; Long Le; Michele McTigue; Gad Getz; Ted W. Johnson; Jeffrey A. Engelman

doi:10.1056/NEJMoa1508887

Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F

Alice T. Shaw, Luc Friboulet, Ignaty Leshchiner, Justin F. Gainor, Simon Bergqvist, Alexei Brooun, Benjamin J. Burke, Ya Li Deng, Wei Liu, Leila Dardaei, Rosa L. Frias, Kate R. Schultz, Jennifer Logan, Leonard P. James, Tod Smeal, Sergei Timofeevski, Ryohei Katayama, A. John Iafrate, Long Le, Michele McTigueGad Getz, Ted W. Johnson, Jeffrey A. Engelman

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Résumé

In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved.

langue originale	Anglais
Pages (de - à)	54-61
Nombre de pages	8
journal	New England Journal of Medicine
Volume	374
Numéro de publication	1
Les DOIs	https://doi.org/10.1056/NEJMoa1508887
état	Publié - 7 janv. 2016
Modification externe	Oui

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10.1056/NEJMoa1508887

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Shaw, A. T., Friboulet, L., Leshchiner, I., Gainor, J. F., Bergqvist, S., Brooun, A., Burke, B. J., Deng, Y. L., Liu, W., Dardaei, L., Frias, R. L., Schultz, K. R., Logan, J., James, L. P., Smeal, T., Timofeevski, S., Katayama, R., Iafrate, A. J., Le, L., ... Engelman, J. A. (2016). Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F. New England Journal of Medicine, 374(1), 54-61. https://doi.org/10.1056/NEJMoa1508887

@article{95536d1368f44abcb291afb2fc44387d,

title = "Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F",

abstract = "In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved.",

author = "Shaw, {Alice T.} and Luc Friboulet and Ignaty Leshchiner and Gainor, {Justin F.} and Simon Bergqvist and Alexei Brooun and Burke, {Benjamin J.} and Deng, {Ya Li} and Wei Liu and Leila Dardaei and Frias, {Rosa L.} and Schultz, {Kate R.} and Jennifer Logan and James, {Leonard P.} and Tod Smeal and Sergei Timofeevski and Ryohei Katayama and Iafrate, {A. John} and Long Le and Michele McTigue and Gad Getz and Johnson, {Ted W.} and Engelman, {Jeffrey A.}",

year = "2016",

month = jan,

day = "7",

doi = "10.1056/NEJMoa1508887",

language = "English",

volume = "374",

pages = "54--61",

journal = "New England Journal of Medicine",

issn = "0028-4793",

number = "1",

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Shaw, AT, Friboulet, L, Leshchiner, I, Gainor, JF, Bergqvist, S, Brooun, A, Burke, BJ, Deng, YL, Liu, W, Dardaei, L, Frias, RL, Schultz, KR, Logan, J, James, LP, Smeal, T, Timofeevski, S, Katayama, R, Iafrate, AJ, Le, L, McTigue, M, Getz, G, Johnson, TW & Engelman, JA 2016, 'Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F', New England Journal of Medicine, VOL. 374, Numéro 1, p. 54-61. https://doi.org/10.1056/NEJMoa1508887

TY - JOUR

T1 - Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F

AU - Shaw, Alice T.

AU - Friboulet, Luc

AU - Leshchiner, Ignaty

AU - Gainor, Justin F.

AU - Bergqvist, Simon

AU - Brooun, Alexei

AU - Burke, Benjamin J.

AU - Deng, Ya Li

AU - Liu, Wei

AU - Dardaei, Leila

AU - Frias, Rosa L.

AU - Schultz, Kate R.

AU - Logan, Jennifer

AU - James, Leonard P.

AU - Smeal, Tod

AU - Timofeevski, Sergei

AU - Katayama, Ryohei

AU - Iafrate, A. John

AU - Le, Long

AU - McTigue, Michele

AU - Getz, Gad

AU - Johnson, Ted W.

AU - Engelman, Jeffrey A.

PY - 2016/1/7

Y1 - 2016/1/7

N2 - In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved.

AB - In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved.

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DO - 10.1056/NEJMoa1508887

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AN - SCOPUS:84954050562

SN - 0028-4793

VL - 374

SP - 54

EP - 61

JO - New England Journal of Medicine

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