Anaplastic Lymphoma Kinase as a Therapeutic Target in Anaplastic Large Cell Lymphoma, Non-Small Cell Lung Cancer and Neuroblastoma

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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Anaplastic Lymphoma Kinase as a Therapeutic Target in Anaplastic Large Cell Lymphoma, Non-Small Cell Lung Cancer and Neuroblastoma

Anti-Cancer Agents in Medicinal Chemistry, 10(3): 236-249.

Author(s): Mangeng Cheng and Gregory R Ott.

Affiliation: Discovery Oncology Research, Cephalon Inc, 145 Brandywine Pkwy, West Chester, PA 19380, USA.


Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase in the insulin receptor superfamily, was originally identified as the oncogenic NPM (nucleophosmin)-ALK fusion protein due to a t (2;5) chromosomal translocation in anaplastic large cell lymphomas. Many other chromosomal rearrangements or gene mutations/amplification leading to enhanced ALK activity have subsequently been identified and characterized in a number of human cancer types. The recent reports of EML4 (echinoderm microtubule-associated protein- like 4)-ALK oncogenic proteins in non-small cell lung cancer (NSCLC) and the identification of ALK activating point mutations and gene amplification in neuroblastoma have indicated ALK as a potential major therapeutic target for human cancers. In this review, the role of oncogenic ALK in development of various human cancers is summarized and the efforts and progress of developing small molecule ALK inhibitors as potential cancer therapeutics are updated. Several small molecule ALK inhibitors from distinctive chemical scaffolds in either clinical or preclinical development stage are highlighted and profiled. The challenges and future directions of developing small molecule ALK inhibitors as cancer therapeutics are discussed.


Anaplastic lymphoma kinase, chromosomal translocation, anaplastic large-cell lymphoma, inflammatory myofibroblastic tumor, non-small cell lung carcinoma, activating mutation, neuroblastoma, tyrosine kinase inhibitor.

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Article Details

Volume: 10
Issue Number: 3
First Page: 236
Last Page: 249
Page Count: 14
DOI: 10.2174/1871520611009030236
Price: $58

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