Anaplastic Lymphoma Kinase: Role in specific tumours, and development of small molecule inhibitors for cancer therapy
Abstract The Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase first identified as the product of a gene rearrangement in Anaplastic Large Cell Lymphoma. ALK has subsequently been found to be rearranged, mutated, or amplified in a further series of tumours including neuroblastoma, and N...
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| Veröffentlicht in: | Cancer letters 2010-12, Vol.299 (2), p.81-94 |
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| container_title | Cancer letters |
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| creator | Ardini, E Magnaghi, P Orsini, P Galvani, A Menichincheri, M |
| description | Abstract The Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase first identified as the product of a gene rearrangement in Anaplastic Large Cell Lymphoma. ALK has subsequently been found to be rearranged, mutated, or amplified in a further series of tumours including neuroblastoma, and Non-Small Cell Lung Cancer. There is strong preclinical evidence that ALK is a driving force for oncogenesis in these cases, and that inhibition of ALK kinase activity results in anti-tumoural efficacy. These observations have sparked the development of small molecule kinase inhibitors, the most advanced of which is currently in clinical testing and which has shown promising preliminary activity in the subset of lung cancer patients whose tumours harbour activated ALK. In this review, we describe the various oncogenic forms of ALK, relevant clinical settings, and give a detailed overview of current drug discovery efforts in the field. |
| doi_str_mv | 10.1016/j.canlet.2010.09.001 |
| format | Article |
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ALK has subsequently been found to be rearranged, mutated, or amplified in a further series of tumours including neuroblastoma, and Non-Small Cell Lung Cancer. There is strong preclinical evidence that ALK is a driving force for oncogenesis in these cases, and that inhibition of ALK kinase activity results in anti-tumoural efficacy. These observations have sparked the development of small molecule kinase inhibitors, the most advanced of which is currently in clinical testing and which has shown promising preliminary activity in the subset of lung cancer patients whose tumours harbour activated ALK. In this review, we describe the various oncogenic forms of ALK, relevant clinical settings, and give a detailed overview of current drug discovery efforts in the field.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2010.09.001</identifier><identifier>PMID: 20934803</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>ALCL ; ALK ; Animals ; Cell growth ; Genetic Predisposition to Disease - genetics ; Hematology, Oncology and Palliative Medicine ; Humans ; Kinase inhibitor ; Kinases ; Molecular Structure ; Mutation ; Neoplasms - drug therapy ; Neoplasms - enzymology ; Neoplasms - genetics ; Neuroblastoma ; NSCLC ; PF-2341066 ; Piperidines - chemistry ; Piperidines - therapeutic use ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Pyrazoles ; Pyridines - chemistry ; Pyridines - therapeutic use ; Pyrimidines - chemistry ; Pyrimidines - therapeutic use ; Pyrroles - chemistry ; Pyrroles - therapeutic use ; Receptor Protein-Tyrosine Kinases ; Rodents</subject><ispartof>Cancer letters, 2010-12, Vol.299 (2), p.81-94</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2010 Elsevier Ireland Ltd</rights><rights>Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Dec 28, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-2e4ecf9b83f4810fe06a969533e8fbaf81cbe8284b2a10179fafb401745da6aa3</citedby><cites>FETCH-LOGICAL-c444t-2e4ecf9b83f4810fe06a969533e8fbaf81cbe8284b2a10179fafb401745da6aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2010.09.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20934803$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ardini, E</creatorcontrib><creatorcontrib>Magnaghi, P</creatorcontrib><creatorcontrib>Orsini, P</creatorcontrib><creatorcontrib>Galvani, A</creatorcontrib><creatorcontrib>Menichincheri, M</creatorcontrib><title>Anaplastic Lymphoma Kinase: Role in specific tumours, and development of small molecule inhibitors for cancer therapy</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract The Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase first identified as the product of a gene rearrangement in Anaplastic Large Cell Lymphoma. ALK has subsequently been found to be rearranged, mutated, or amplified in a further series of tumours including neuroblastoma, and Non-Small Cell Lung Cancer. There is strong preclinical evidence that ALK is a driving force for oncogenesis in these cases, and that inhibition of ALK kinase activity results in anti-tumoural efficacy. These observations have sparked the development of small molecule kinase inhibitors, the most advanced of which is currently in clinical testing and which has shown promising preliminary activity in the subset of lung cancer patients whose tumours harbour activated ALK. In this review, we describe the various oncogenic forms of ALK, relevant clinical settings, and give a detailed overview of current drug discovery efforts in the field.</description><subject>ALCL</subject><subject>ALK</subject><subject>Animals</subject><subject>Cell growth</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Kinase inhibitor</subject><subject>Kinases</subject><subject>Molecular Structure</subject><subject>Mutation</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Neoplasms - genetics</subject><subject>Neuroblastoma</subject><subject>NSCLC</subject><subject>PF-2341066</subject><subject>Piperidines - chemistry</subject><subject>Piperidines - therapeutic use</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Pyrazoles</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - therapeutic use</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - therapeutic use</subject><subject>Pyrroles - chemistry</subject><subject>Pyrroles - therapeutic use</subject><subject>Receptor Protein-Tyrosine Kinases</subject><subject>Rodents</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkluLFDEQhYMo7rj6D0QCPvhij5VLd6d9EJbFGw4IXp5DOl1hMqY7bdK9MP_ejLMq7ItPCeE7lapzipCnDLYMWPPqsLVmCrhsOZQn6LYA7B7ZMNXyqu0U3CcbECAroUR9QR7lfACAWrb1Q3LBoRNSgdiQ9WoyczB58ZbujuO8j6Ohn_xkMr6mX2JA6ieaZ7TeFWJZx7im_JKaaaAD3mCI84jTQqOjeTQh0LFI7Ppbtve9X2LK1MVES68WE132mMx8fEweOBMyPrk9L8n3d2-_XX-odp_ff7y-2lVWSrlUHCVa1_VKOKkYOITGdE1XC4HK9cYpZntUXMmem-JJ2znjelkush5MY4y4JC_OdecUf66YFz36bDEEM2Fcs24bDsULJQr5_A55KJNOpTnN6pq1vJFMFUqeKZtizgmdnpMfTTpqBvqUij7ocyr6lIqGTpdUiuzZbfG1H3H4K_oTQwHenAEsZtx4TDpbj8WxwSe0ix6i_98PdwvY4CdvTfiBR8z_ZtGZa9BfT5txWgxWdkJyIcUviLW1jg</recordid><startdate>20101228</startdate><enddate>20101228</enddate><creator>Ardini, E</creator><creator>Magnaghi, P</creator><creator>Orsini, P</creator><creator>Galvani, A</creator><creator>Menichincheri, M</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20101228</creationdate><title>Anaplastic Lymphoma Kinase: Role in specific tumours, and development of small molecule inhibitors for cancer therapy</title><author>Ardini, E ; Magnaghi, P ; Orsini, P ; Galvani, A ; Menichincheri, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-2e4ecf9b83f4810fe06a969533e8fbaf81cbe8284b2a10179fafb401745da6aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>ALCL</topic><topic>ALK</topic><topic>Animals</topic><topic>Cell growth</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Kinase inhibitor</topic><topic>Kinases</topic><topic>Molecular Structure</topic><topic>Mutation</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Neoplasms - genetics</topic><topic>Neuroblastoma</topic><topic>NSCLC</topic><topic>PF-2341066</topic><topic>Piperidines - chemistry</topic><topic>Piperidines - therapeutic use</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Pyrazoles</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - therapeutic use</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - therapeutic use</topic><topic>Pyrroles - chemistry</topic><topic>Pyrroles - therapeutic use</topic><topic>Receptor Protein-Tyrosine Kinases</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ardini, E</creatorcontrib><creatorcontrib>Magnaghi, P</creatorcontrib><creatorcontrib>Orsini, P</creatorcontrib><creatorcontrib>Galvani, A</creatorcontrib><creatorcontrib>Menichincheri, M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ardini, E</au><au>Magnaghi, P</au><au>Orsini, P</au><au>Galvani, A</au><au>Menichincheri, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anaplastic Lymphoma Kinase: Role in specific tumours, and development of small molecule inhibitors for cancer therapy</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2010-12-28</date><risdate>2010</risdate><volume>299</volume><issue>2</issue><spage>81</spage><epage>94</epage><pages>81-94</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract The Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase first identified as the product of a gene rearrangement in Anaplastic Large Cell Lymphoma. 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| issn | 0304-3835 1872-7980 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | ALCL ALK Animals Cell growth Genetic Predisposition to Disease - genetics Hematology, Oncology and Palliative Medicine Humans Kinase inhibitor Kinases Molecular Structure Mutation Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - genetics Neuroblastoma NSCLC PF-2341066 Piperidines - chemistry Piperidines - therapeutic use Protein-Tyrosine Kinases - antagonists & inhibitors Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Pyrazoles Pyridines - chemistry Pyridines - therapeutic use Pyrimidines - chemistry Pyrimidines - therapeutic use Pyrroles - chemistry Pyrroles - therapeutic use Receptor Protein-Tyrosine Kinases Rodents |
| title | Anaplastic Lymphoma Kinase: Role in specific tumours, and development of small molecule inhibitors for cancer therapy |
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