Anaplastic lymphoma kinase as a therapeutic target
A Kruczynski, G Delsol, C Laurent… - Expert opinion on …, 2012 - Taylor & Francis
A Kruczynski, G Delsol, C Laurent, P Brousset, L Lamant
Expert opinion on therapeutic targets, 2012•Taylor & FrancisIntroduction: Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, has been
initially identified through its involvement in chromosomal translocations associated with
anaplastic large cell lymphoma. However, recent evidence that aberrant ALK activity is also
involved in an expanding number of tumor types, such as other lymphomas, inflammatory
myofibroblastic tumor, neuroblastomas and some carcinomas, including non-small cell lung
carcinomas, is boosting research progress in ALK-targeted therapies. Areas covered: The …
initially identified through its involvement in chromosomal translocations associated with
anaplastic large cell lymphoma. However, recent evidence that aberrant ALK activity is also
involved in an expanding number of tumor types, such as other lymphomas, inflammatory
myofibroblastic tumor, neuroblastomas and some carcinomas, including non-small cell lung
carcinomas, is boosting research progress in ALK-targeted therapies. Areas covered: The …
Introduction: Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, has been initially identified through its involvement in chromosomal translocations associated with anaplastic large cell lymphoma. However, recent evidence that aberrant ALK activity is also involved in an expanding number of tumor types, such as other lymphomas, inflammatory myofibroblastic tumor, neuroblastomas and some carcinomas, including non-small cell lung carcinomas, is boosting research progress in ALK-targeted therapies.
Areas covered: The first aim of this review is to describe current understandings about the ALK tyrosine kinase and its implication in the oncogenesis of human cancers as a fusion protein or through mutations. The second goal is to discuss its interest as a therapeutic target and to provide a review of the literature regarding ALK inhibitors. Mechanisms of acquired resistance are also reviewed.
Expert opinion: Several ALK inhibitors have recently been developed, offering new treatment options in tumors driven by abnormal ALK signaling. However, as observed with other tyrosine kinase inhibitors, resistance has emerged in patients treated with these agents. The complexity of mechanisms of acquired resistance recently described suggests that other therapeutic options, including combination of ALK and other kinases targeted drugs, will be required in the future.
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