EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors

被引：894

作者：

Choi, Young Lim ^{[1
,2
]}

Soda, Manabu ^{[1
]}

Yamashita, Yoshihiro ^{[1
]}

Ueno, Toshihide ^{[1
]}

Takashima, Junpei ^{[3
]}

Nakajima, Takahiro ^{[4
]}

Yatabe, Yasushi ^{[5
]}

Takeuchi, Kengo ^{[7
]}

Hamada, Toru ^{[1
]}

Haruta, Hidenori ^{[1
]}

Ishikawa, Yuichi ^{[8
]}

Kimura, Hideki ^{[4
]}

Mitsudomi, Tetsuya ^{[6
]}

Tanio, Yoshiro ^{[3
]}

Mano, Hiroyuki ^{[1
,2
,9
]}

机构：

[1] Jichi Med Univ, Div Funct Genom, Shimotsuke, Tochigi 3290498, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Med Genom, Tokyo, Japan

[3] Osaka Gen Med Ctr, Dept Internal Med, Osaka, Japan

[4] Chiba Canc Ctr, Div Thorac Dis, Chiba 2608717, Japan

[5] Aichi Canc Ctr Hosp, Dept Pathol, Aichi, Japan

[6] Aichi Canc Ctr Hosp, Dept Thorac Surg, Aichi, Japan

[7] Japanese Fdn Canc Res, Inst Canc, Pathol Project Mol Targets, Tokyo 170, Japan

[8] Japanese Fdn Canc Res, Inst Canc, Div Pathol, Tokyo 170, Japan

[9] Japan Sci & Technol Agcy, Saitama, Japan

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 363卷 / 18期

基金：

日本学术振兴会;

关键词：

CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE; ACQUIRED-RESISTANCE; IMATINIB; IDENTIFICATION; GEFITINIB; FUSION; DOMAIN; ABL; EFFICACY;

D O I：

10.1056/NEJMoa1007478

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors.

引用

页码：1734 / 1739

页数：6

共 20 条

[1] Crystal Structures of Anaplastic Lymphoma Kinase in Complex with ATP Competitive Inhibitors
Bossi, Roberto T.
Saccardo, M. Beatrice
Ardini, Elena
Menichincheri, Maria
Rusconi, Luisa
Magnaghi, Paola
Orsini, Paolo
Avanzi, Nilla
Borgia, Andrea Lombardi
Nesi, Marcella
Bandiera, Tiziano
Fogliatto, Gianpaolo
Bertrand, Jay A.
[J]. BIOCHEMISTRY, 2010, 49 (32) : 6813 - 6825
[2] Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter?
Branford, Susan
Melo, Junia V.
Hughes, Timothy P.
[J]. BLOOD, 2009, 114 (27) : 5426 - 5435
[3] Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases
Carter, TA
Wodicka, LM
Shah, NP
Velasco, AM
Fabian, MA
Treiber, DK
Milanov, ZV
Atteridge, CE
Biggs, WH
Edeen, PT
Floyd, M
Ford, JM
Grotzfeld, RM
Herrgard, S
Insko, DE
Mehta, SA
Patel, HK
Pao, W
Sawyers, CL
Varmus, H
Zarrinkar, PP
Lockhart, DJ
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (31) : 11011 - 11016
[4] Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer
Choi, Young Lim
Takeuchi, Kengo
Soda, Manabu
Inamura, Kentaro
Togashi, Yuki
Hatano, Satoko
Enomoto, Munehiro
Hamada, Toru
Haruta, Hidenori
Watanabe, Hideki
Kurashina, Kentaro
Hatanaka, Hisashi
Ueno, Toshihide
Takada, Shuji
Yamashita, Yoshihiro
Sugiyama, Yukihiko
Ishikawa, Yuichi
Mano, Hiroyuki
[J]. CANCER RESEARCH, 2008, 68 (13) : 4971 - 4976
[5] Identification of a constitutively active mutant of JAK3 by retroviral expression screening
Choi, Young Lim
Kaneda, Ruri
Wada, Tomoaki
Fujiwara, Shin-ichiro
Soda, Manabu
Watanabe, Hideki
Kurashina, Kentaro
Hatanaka, Hisashi
Enomoto, Munehiro
Takada, Shuji
Yamashita, Yoshihiro
Mano, Hiroyuki
[J]. LEUKEMIA RESEARCH, 2007, 31 (02) : 203 - 209
[6] A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome
Cools, J
DeAngelo, DJ
Gotlib, J
Stover, EH
Legare, RD
Cortes, J
Kutok, J
Clark, J
Galinsky, I
Griffin, JD
Cross, NCP
Tefferi, A
Malone, J
Alam, R
Schrier, SL
Schmid, J
Rose, M
Vandenberghe, P
Verhoef, G
Boogaerts, M
Wlodarska, I
Kantarjian, H
Marynen, P
Coutre, SE
Stone, R
Gilliland, DG
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (13) : 1201 - 1214
[7] The development of imatinib as a therapeutic agent for chronic myeloid leukemia
Deininger, M
Buchdunger, E
Druker, BJ
[J]. BLOOD, 2005, 105 (07) : 2640 - 2653
[8] Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.
Druker, BJ
Talpaz, M
Resta, DJ
Peng, B
Buchdunger, E
Ford, JM
Lydon, NB
Kantarjian, H
Capdeville, R
Ohno-Jones, S
Sawyers, CL
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) : 1031 - 1037
[9] Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1
Hindie, Valerie
Stroba, Adriana
Zhang, Hua
Lopez-Garcia, Laura A.
Idrissova, Leila
Zeuzem, Stefan
Hirschberg, Daniel
Schaeffer, Francis
Jorgensen, Thomas J. D.
Engel, Matthias
Alzari, Pedro M.
Biondi, Ricardo M.
[J]. NATURE CHEMICAL BIOLOGY, 2009, 5 (10) : 758 - 764
[10] EML4-ALK: Honing In on a New Target in Non-Small-Cell Lung Cancer
Horn, Leora
Pao, William
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (26) : 4232 - 4235

← 1 2 →