A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer

Wilson, Frederick H.; Johannessen, Cory M.; Piccioni, Federica; Tamayo, Pablo; Kim, Jong Wook; Van Allen, Eliezer M.; Corsello, Steven M.; Capelletti, Marzia; Calles, Antonio; Butaney, Mohit; Sharifnia, Tanaz; Gabriel, Stacey B.; Mesirov, Jill P.; Hahn, William C.; Engelman, Jeffrey A.; Meyerson, Matthew; Root, David E.; Jänne, Pasi A.; Garraway, Levi A.

doi:10.1016/j.ccell.2015.02.005

Back to Previous Page

- Add this to...
- Twitter
- Facebook
- Google Bookmarks
- LinkedIn

A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer

Published Date:

Mar 9 2015

Publisher's site:

http://dx.doi.org/10.1016/j.ccell.2015.02.005 New Site Icon

Source:

Cancer Cell. 2015; 27(3):397-408.

[PDF-2.41 MB]

Details:

Personal Authors:

Wilson, Frederick H. ; Johannessen, Cory M. ; Piccioni, Federica ; Tamayo, Pablo ; Kim, Jong Wook ; ... More ▼

Keywords:

[+]

Pubmed ID:

25759024

Pubmed Central ID:

PMC4398996

Description:

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.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

Supporting Files:

	nihms669094f2.gif	image/gif
	nihms669094f2.jpg	image/jpeg
	nihms669094f3.gif	image/gif
	nihms669094f3.jpg	image/jpeg
	nihms669094f4.gif	image/gif
	nihms669094f4.jpg	image/jpeg
	nihms669094f5.gif	image/gif
	nihms669094f5.jpg	image/jpeg
	nihms669094f6.gif	image/gif
	nihms669094f6.jpg	image/jpeg
	NIHMS669094-supplement-1.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
	nihms669094f7.gif	image/gif
	nihms669094f7.jpg	image/jpeg
	NIHMS669094-supplement-2.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
	NIHMS669094-supplement-3.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
	NIHMS669094-supplement-4.pdf	application/pdf
	NIHMS669094-supplement-5.pdf	application/pdf
	nihms669094.nxml	application/octet-stream
	nihms669094f1.gif	image/gif
	nihms669094f1.jpg	image/jpeg

No Related Documents.

You May Also Like:

Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Personal Author:

Dizon, Don S.; Krilov, Lada; Cohen, Ezra; Gangadhar, Tara; Ganz, Patricia A.; Hensing, Thomas A.; Hunger, Stephen; Krishnamurthi, Smitha S.; Lassman, Andrew B.; Markham, Merry Jennifer; Mayer, Erica; Neuss, Michael; Pal, Sumanta Kumar; Richardson, Lisa C.; Schilsky, Richard; Schwartz, Gary K.; Spriggs, David R.; Villalona-Calero, Miguel Angel; Villani, Gina; Masters, Gregory;

Published:

Feb 04 2016

Source:

J Clin Oncol. 34(9):987-1011.

File Type:

[PDF - 692.37 KB]
Wnt signaling in triple negative breast cancer is associated with metastasis

Personal Author:

Dey, Nandini; Barwick, Benjamin G; Moreno, Carlos S; Ordanic-Kodani, Maja; Chen, Zhengjia; Oprea-Ilies, Gabriella; Tang, Weining; Catzavelos, Charles; Kerstann, Kimberly F; Sledge, George W; Abramovitz, Mark; Bouzyk, Mark; De, Pradip; Leyland-Jones, Brian R;

Published:

Nov 10 2013

Source:

BMC Cancer. 2013; 13:537.

Description:

Background : Triple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment optio...

File Type:

[PDF - 1.82 MB]
Safe Handling of Oral Antineoplastic Medications: Focus on Targeted Therapeutics in the Home Setting

Personal Author:

Cass, Yaakov; Connor, Thomas H.; Tabachnik, Alexander;

Published:

Mar 22 2016

Source:

J Oncol Pharm Pract. 23(5):350-378.

Description:

Introduction : With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the ...

File Type:

[PDF - 448.42 KB]
Combination of Protein Coding and Noncoding Gene Expression as a Robust Prognostic Classifier in Stage I Lung Adenocarcinoma

Personal Author:

Akagi, Ichiro; Okayama, Hirokazu; Schetter, Aaron J.; Robles, Ana I.; Kohno, Takashi; Bowman, Elise D.; Kazandjian, Dickran; Welsh, Judith A.; Oue, Naohide; Saito, Motonobu; Miyashita, Masao; Uchida, Eiji; Takizawa, Toshihiro; Takenoshita, Seiichi; Skaug, Vidar; Mollerup, Steen; Haugen, Aage; Yokota, Jun; Harris, Curtis C.;

Published:

May 02 2013

Source:

Cancer Res. 73(13):3821-3832

Description:

Prognostic tests for patients with early-stage lung cancer may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early-stage lung cancer. Spec...

File Type:

[PDF - 1.16 MB]
HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia

Personal Author:

Akahane, Koshi; Sanda, Takaomi; Mansour, Marc R.; Radimerski, Thomas; DeAngelo, Daniel J.; Weinstock, David M.; Look, A. Thomas;

Published:

Aug 12 2015

Source:

Leukemia. 30(1):219-228.

Description:

We previously found that tyrosine kinase 2 (TYK2) signaling through its downstream effector phospho-STAT1 acts to upregulate BCL2, which in turn mediates aberrant survival of T-cell acute lymphoblastic leukemia (T-ALL) cells. Here we show that pharma...

File Type:

[PDF - 1.88 MB]