EML4-ALK fusions: Propelling cancer but creating exploitable chaperone dependence

Cancer Discovery

Volumn 4, Issue 6, 2014, Pages 642-645

  Workman, Paul ^a   van Montfort, Rob ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; CELL CYCLE PROTEIN 37; CHAPERONE; CRIZOTINIB; EML4 ALK PROTEIN; GANETESPIB; GLOBULAR PROTEIN; HEAT SHOCK PROTEIN 90; HYBRID PROTEIN; INTERLEUKIN 3; MICROTUBULE ASSOCIATED PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN VARIANT; TUBULIN; UNCLASSIFIED DRUG; EML1 PROTEIN, HUMAN; EML4-ALK FUSION PROTEIN, HUMAN; ONCOPROTEIN;

ARTICLE; AUTOPHOSPHORYLATION; CANCER INHIBITION; CARBOXY TERMINAL SEQUENCE; CELL GROWTH; CRYSTAL STRUCTURE; GENOTYPE; HUMAN; LUNG NON SMALL CELL CANCER; NONHUMAN; OLIGOMERIZATION; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN LOCALIZATION; TUMOR XENOGRAFT; X RAY CRYSTALLOGRAPHY; ANIMAL; CHEMISTRY; LUNG TUMOR; METABOLISM; NON SMALL CELL LUNG CANCER; PROTEIN CONFORMATION;

ANIMALS; CARCINOMA, NON-SMALL-CELL LUNG; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LUNG NEOPLASMS; MICROTUBULE-ASSOCIATED PROTEINS; ONCOGENE PROTEINS, FUSION; PROTEIN CONFORMATION;

EID: 84904055782     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-14-0409     Document Type: Article

References (10)

1. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448: 561-6.
2. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010; 363: 1693-703.
3. Katayama R, Khan TM, Benes C, Lifshits E, Ebi H, Rivera VM, et al. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A 2011; 108: 7535-40.
4. Sang J, Acquaviva J, Friedland JC, Smith DL, Sequeira M, Zhang C, et al. Targeted inhibition of the molecular chaperone Hsp90 overcomes ALK inhibitor resistance in non-small cell lung cancer. Cancer Discov 2013; 4: 430-43.
5. Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 2012; 18: 64-76.
6. Sequist LV, Gettinger S, Senzer NN, Martins RG, Jänne PA, Lilenbaum R, et al. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol 2010; 33: 4953-60.
7. Richards MW, Law EW, Rennalls LP, Busacca S, O'Regan L, Fry AM, et al. Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical o-propeller domain. Proc Natl Acad Sci U S A 2014; 14: 5195-200.
8. Paoli M. Protein folds propelled by diversity. Prog Mol Biol Biophys 2001; 76: 103-30.
9. Hegyi H, Buday L, Tompa P. Intrinsic structural disorder confers cellular viability on oncogenic fusion proteins. PLOS Comput Biol 2009; 5: 1000552.
10. Taipale M, Krykbaeva I, Koeva M, Kayatekin C, Westover KD, Karras GI, et al. Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 2012; 150: 987-1001.