Anaplastic lymphoma kinase fusions: Roles in cancer and therapeutic perspectives (Review)

Published on Dec 20, 2018in Oncology Letters2.967
· DOI :10.3892/OL.2018.9856
Zhi-Fa Cao2
Estimated H-index: 2
(ZSTU: Zhejiang Sci-Tech University),
Qian Gao1
Estimated H-index: 1
(NKU: Nankai University)
+ 3 AuthorsWen-Bin Ou24
Estimated H-index: 24
(ZSTU: Zhejiang Sci-Tech University)
Sources
Abstract
: Receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) serves a crucial role in brain development. ALK is located on the short arm of chromosome 2 (2p23) and exchange of chromosomal segments with other genes, including nucleophosmin (NPM), echinoderm microtubule-associated protein-like 4 (EML4) and Trk-fused gene (TFG), readily occurs. Such chromosomal translocation results in the formation of chimeric X-ALK fusion oncoproteins, which possess potential oncogenic functions due to constitutive activation of ALK kinase. These proteins contribute to the pathogenesis of various hematological malignancies and solid tumors, including lymphoma, lung cancer, inflammatory myofibroblastic tumors (IMTs), Spitz tumors, renal carcinoma, thyroid cancer, digestive tract cancer, breast cancer, leukemia and ovarian carcinoma. Targeting of ALK fusion oncoproteins exclusively, or in combination with ALK kinase inhibitors including crizotinib, is the most common therapeutic strategy. As is often the case for small-molecule tyrosine kinase inhibitors (TKIs), drug resistance eventually develops via an adaptive secondary mutation in the ALK fusion oncogene, or through engagement of alternative signaling mechanisms. The updated mechanisms of a variety of ALK fusions in tumorigenesis, proliferation and metastasis, in addition to targeted therapies are discussed below.
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References133
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#1Christine J. Ye (UM: University of Michigan)H-Index: 26
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Last. Henry H.Q. Heng (WSU: Wayne State University)H-Index: 71
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Background In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of...
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#1Mathew Bloomfield (University of California, Berkeley)H-Index: 6
#2Peter H. Duesberg (University of California, Berkeley)H-Index: 78
Foulds defined, “Tumor progression (as a) permanent, irreversible qualitative change in one or more of its characters” (Cancer Res. 1954). Accordingly progressions, such as metastases and acquired drug-resistance, were since found to be subspecies of cancers with conserved and numerous new chromosomes. Here we ask whether cancers acquire numerous new chromosomes gradually or simultaneously in progressions. The currently prevailing theory of Nowell (Science, 1976) holds that unexplained “genetic ...
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#1Sulman Basit (Taibah University)H-Index: 20
#2Zaman Ashraf (Allama Iqbal Open University)H-Index: 17
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#1An Na Seo (KNU: Kyungpook National University)H-Index: 2
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#1Yoko ShimadaH-Index: 20
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#2Wei Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 88
// Shaohua Cui 1, * , Wei Zhang 1, * , Liwen Xiong 1 , Feng Pan 1 , Yanjie Niu 1 , Tianqing Chu 1 , Huimin Wang 1 , Yizhuo Zhao 1 , Liyan Jiang 1 1 Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China * These authors contributed equally to this work Correspondence to: Liyan Jiang, email: Jiang_liyan2000@126.com Yizhuo Zhao, email: zhyz920916@126.com Keywords: liquid biopsy, anaplastic lymphoma kinase (ALK), capture-based next-generation sequ...
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#1Vijaykumar Holla (University of Texas MD Anderson Cancer Center)H-Index: 16
#2Yasir Elamin (University of Texas MD Anderson Cancer Center)H-Index: 14
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#1Mathew Bloomfield (University of California, Berkeley)H-Index: 6
#2Peter H. Duesberg (University of California, Berkeley)H-Index: 78
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AbstractIntroduction: Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, has been discovered in several cancers, including anaplastic large-cell lymphoma, non-small cell lung cancer and ...
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