Acquired resistance to crizotinib from a mutation in CD74-ROS1

Mark M. Awad; Ryohei Katayama; Michele McTigue; Wei Liu; Ya Li Deng; Alexei Brooun; Luc Friboulet; Donghui Huang; Matthew D. Falk; Sergei Timofeevski; Keith D. Wilner; Elizabeth L. Lockerman; Tahsin M. Khan; Sidra Mahmood; Justin F. Gainor; Subba R. Digumarthy; James R. Stone; Mari Mino-Kenudson; James G. Christensen; A. John Iafrate; Jeffrey A. Engelman; Alice T. Shaw

doi:10.1056/NEJMoa1215530

Acquired resistance to crizotinib from a mutation in CD74-ROS1

Mark M. Awad, Ryohei Katayama, Michele McTigue, Wei Liu, Ya Li Deng, Alexei Brooun, Luc Friboulet, Donghui Huang, Matthew D. Falk, Sergei Timofeevski, Keith D. Wilner, Elizabeth L. Lockerman, Tahsin M. Khan, Sidra Mahmood, Justin F. Gainor, Subba R. Digumarthy, James R. Stone, Mari Mino-Kenudson, James G. Christensen, A. John IafrateJeffrey A. Engelman, Alice T. Shaw

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Résumé

Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)

langue originale	Anglais
Pages (de - à)	2395-2401
Nombre de pages	7
journal	New England Journal of Medicine
Volume	368
Numéro de publication	25
Les DOIs	https://doi.org/10.1056/NEJMoa1215530
état	Publié - 1 janv. 2013
Modification externe	Oui

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10.1056/NEJMoa1215530

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Awad, M. M., Katayama, R., McTigue, M., Liu, W., Deng, Y. L., Brooun, A., Friboulet, L., Huang, D., Falk, M. D., Timofeevski, S., Wilner, K. D., Lockerman, E. L., Khan, T. M., Mahmood, S., Gainor, J. F., Digumarthy, S. R., Stone, J. R., Mino-Kenudson, M., Christensen, J. G., ... Shaw, A. T. (2013). Acquired resistance to crizotinib from a mutation in CD74-ROS1. New England Journal of Medicine, 368(25), 2395-2401. https://doi.org/10.1056/NEJMoa1215530

@article{5f146a1b7ec34667958222860ccded15,

title = "Acquired resistance to crizotinib from a mutation in CD74-ROS1",

abstract = "Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)",

author = "Awad, {Mark M.} and Ryohei Katayama and Michele McTigue and Wei Liu and Deng, {Ya Li} and Alexei Brooun and Luc Friboulet and Donghui Huang and Falk, {Matthew D.} and Sergei Timofeevski and Wilner, {Keith D.} and Lockerman, {Elizabeth L.} and Khan, {Tahsin M.} and Sidra Mahmood and Gainor, {Justin F.} and Digumarthy, {Subba R.} and Stone, {James R.} and Mari Mino-Kenudson and Christensen, {James G.} and Iafrate, {A. John} and Engelman, {Jeffrey A.} and Shaw, {Alice T.}",

year = "2013",

month = jan,

day = "1",

doi = "10.1056/NEJMoa1215530",

language = "English",

volume = "368",

pages = "2395--2401",

journal = "New England Journal of Medicine",

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Awad, MM, Katayama, R, McTigue, M, Liu, W, Deng, YL, Brooun, A, Friboulet, L, Huang, D, Falk, MD, Timofeevski, S, Wilner, KD, Lockerman, EL, Khan, TM, Mahmood, S, Gainor, JF, Digumarthy, SR, Stone, JR, Mino-Kenudson, M, Christensen, JG, Iafrate, AJ, Engelman, JA & Shaw, AT 2013, 'Acquired resistance to crizotinib from a mutation in CD74-ROS1', New England Journal of Medicine, VOL. 368, Numéro 25, p. 2395-2401. https://doi.org/10.1056/NEJMoa1215530

TY - JOUR

T1 - Acquired resistance to crizotinib from a mutation in CD74-ROS1

AU - Awad, Mark M.

AU - Katayama, Ryohei

AU - McTigue, Michele

AU - Liu, Wei

AU - Deng, Ya Li

AU - Brooun, Alexei

AU - Friboulet, Luc

AU - Huang, Donghui

AU - Falk, Matthew D.

AU - Timofeevski, Sergei

AU - Wilner, Keith D.

AU - Lockerman, Elizabeth L.

AU - Khan, Tahsin M.

AU - Mahmood, Sidra

AU - Gainor, Justin F.

AU - Digumarthy, Subba R.

AU - Stone, James R.

AU - Mino-Kenudson, Mari

AU - Christensen, James G.

AU - Iafrate, A. John

AU - Engelman, Jeffrey A.

AU - Shaw, Alice T.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)

AB - Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)

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