A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer

被引：153

作者：

Wilson, Frederick H. ^{[1
,2
]}

Johannessen, Cory M. ^{[2
]}

Piccioni, Federica ^{[2
]}

Tamayo, Pablo ^{[2
]}

Kim, Jong Wook ^{[1
,2
]}

Van Allen, Eliezer M. ^{[1
,2
]}

Corsello, Steven M. ^{[1
,2
]}

Capelletti, Marzia ^{[1
]}

Calles, Antonio ^{[1
]}

Butaney, Mohit ^{[1
]}

Sharifnia, Tanaz ^{[1
,2
]}

Gabriel, Stacey B. ^{[2
]}

Mesirov, Jill P. ^{[2
]}

Hahn, William C. ^{[1
,2
]}

Engelman, Jeffrey A. ^{[3
]}

Meyerson, Matthew ^{[1
,2
,4
]}

Root, David E. ^{[2
]}

Jaenne, Pasi A. ^{[1
,5
]}

Garraway, Levi A. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[4] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA

来源：

CANCER CELL | 2015年 / 27卷 / 03期

关键词：

CRIZOTINIB RESISTANCE; ACQUIRED-RESISTANCE; TARGETED THERAPY; KINASE; RECEPTOR; ACTIVATION; EXPRESSION; GENE; PHOSPHORYLATION; PROLIFERATION;

D O I：

10.1016/j.ccell.2015.02.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We conducted a large-scale functional genetic study to characterize mechanisms of resistance to ALK inhibition in ALK-dependent lung cancer cells. We identify members of known resistance pathways and additional putative resistance drivers. Among the latter were members of the P2Y purinergic receptor family of G-protein-coupled receptors (P2Y1, P2Y2, and P2Y6). P2Y receptors mediated resistance in part through a protein-kinase-C (PKC)-dependent mechanism. Moreover, PKC activation alone was sufficient to confer resistance to ALK inhibitors, whereas combined ALK and PKC inhibition restored sensitivity. We observed enrichment of gene signatures associated with several resistance drivers (including P2Y receptors) in crizotinib-resistant ALK-rearranged lung tumors compared to treatment-naive controls, supporting a role for these identified mechanisms in clinical ALK inhibitor resistance.

引用

页码：397 / 408

页数：12

共 51 条

[1] Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation [J].

Amin, Ruhul ;

Sharma, Sapna ;

Ratakonda, Sireesha ;

Hassan, Hatim A. .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2013, 305 (01) :C78-C89

[2] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[3] The participation of plasma membrane hemichannels to purinergic signaling [J].

Baroja-Mazo, Alberto ;

Barbera-Cremades, Maria ;

Pelegrin, Pablo .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2013, 1828 (01) :79-93

[4] Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives [J].

Buder, Kristina ;

Gesierich, Anja ;

Gelbrich, Goetz ;

Goebeler, Matthias .

CANCER MEDICINE, 2013, 2 (05) :674-686

[5] Nucleotide P2Y1 receptor regulates EGF receptor mitogenic signaling and expression in epithelial cells [J].

Buvinic, Sonja ;

Bravo-Zehnder, Marcela ;

Boyer, Jose Luis ;

Huidobro-Toro, Juan Pablo ;

Gonzalez, Alfonso .

JOURNAL OF CELL SCIENCE, 2007, 120 (24) :4289-4301

[6] Amplification of CRKL Induces Transformation and Epidermal Growth Factor Receptor Inhibitor Resistance in Human Non-Small Cell Lung Cancers [J].

Cheung, Hiu Wing ;

Du, Jinyan ;

Boehm, Jesse S. ;

He, Frank ;

Weir, Barbara A. ;

Wang, Xiaoxing ;

Butaney, Mohit ;

Sequist, Lecia V. ;

Luo, Biao ;

Engelman, Jeffrey A. ;

Root, David E. ;

Meyerson, Matthew ;

Golub, Todd R. ;

Jaenne, Pasi A. ;

Hahn, William C. .

CANCER DISCOVERY, 2011, 1 (07) :608-625

[7] EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors [J].

Choi, Young Lim ;

Soda, Manabu ;

Yamashita, Yoshihiro ;

Ueno, Toshihide ;

Takashima, Junpei ;

Nakajima, Takahiro ;

Yatabe, Yasushi ;

Takeuchi, Kengo ;

Hamada, Toru ;

Haruta, Hidenori ;

Ishikawa, Yuichi ;

Kimura, Hideki ;

Mitsudomi, Tetsuya ;

Tanio, Yoshiro ;

Mano, Hiroyuki .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (18) :1734-1739

[8] Activation of mitogen-activated protein kinase in estrogen receptor α-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor α-negative human breast tumors [J].

Creighton, CJ ;

Hilger, AM ;

Murthy, S ;

Rae, JM ;

Chinnaiyan, AM ;

El-Ashry, D .

CANCER RESEARCH, 2006, 66 (07) :3903-3911

[9] Patient-derived models of acquired resistance can identify effective drug combinations for cancer [J].

Crystal, Adam S. ;

Shaw, Alice T. ;

Sequist, Lecia V. ;

Friboulet, Luc ;

Niederst, Matthew J. ;

Lockerman, Elizabeth L. ;

Frias, Rosa L. ;

Gainor, Justin F. ;

Amzallag, Arnaud ;

Greninger, Patricia ;

Lee, Dana ;

Kalsy, Anuj ;

Gomez-Caraballo, Maria ;

Elamine, Leila ;

Howe, Emily ;

Hur, Wooyoung ;

Lifshits, Eugene ;

Robinson, Hayley E. ;

Katayama, Ryohei ;

Faber, Anthony C. ;

Awad, Mark M. ;

Ramaswamy, Sridhar ;

Mino-Kenudson, Mari ;

Iafrate, A. John ;

Benes, Cyril H. ;

Engelman, Jeffrey A. .

SCIENCE, 2014, 346 (6216) :1480-1486

[10] Purines, Purinergic Receptors, and Cancer [J].

Di Virgilio, Francesco .

CANCER RESEARCH, 2012, 72 (21) :5441-5447

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