Anaplastic lymphoma kinase: Role in cancer and therapy perspective

Abstract

Anaplastic lymphoma kinase (ALK) is correlated with oncogenesis in different types of cancers, such as anaplastic large cell lymphoma, lung cancer, neuroblastoma, and even breast cancer, by abnormal fusion of ALK or non-fusion ALK activation. ALK is a receptor tyrosine kinase, with a single transmembrane domain, that plays an important role in development. Upon ligand binding to the extracellular domain, the receptor undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. In recent years, ALK inhibitors have been developed for cancer treatment. These inhibitors target ALK activity and show effectiveness in ALK-positive non-small cell lung cancer. However, acquired treatment resistance makes the future of this therapy unclear; new strategies are underway to overcome the limitations of current ALK inhibitors.

Keywords: anaplastic lymphoma kinase; cancer; inhibitor; resistance; therapy; tyrosine kinase.

Figures

Figure 1.

The ALK receptor kinase: its domains, fusion break point, mutations, and resistance mutations. Reproduced with modification from Wellstein A, Toretsky JA. Hunting ALK to feed targeted cancer therapy. Nat Med. 2011; 17: 290–1. PMID: 21383740; doi: 10.1038/nm0311–290. © 2011 Nature America, Inc. By permission.

Figure 2.

The ALK receptor kinase signaling pathways.

Figure 3.

The ALK receptor kinase: fusion proteins. Reproduced with modification from Ardini E, Magnaghi P, Orsini P, Galvani A, Menichincheri M. Anaplastic Lymphoma Kinase: role in specific tumors, and development of small molecule inhibitors for cancer therapy. Cancer Lett 2010; 299: 81–94. PMID: 20934803; doi: 10.1016/j.canlet.2010.09.001. © 2010 Elsevier Ireland Ltd. By permission.