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Publication : Targeting ALK: Precision Medicine Takes on Drug Resistance.

First Author  Lin JJ Year  2017
Journal  Cancer Discov Volume  7
Issue  2 Pages  137-155
PubMed ID  28122866 Mgi Jnum  J:239601
Mgi Id  MGI:5829298 Doi  10.1158/2159-8290.CD-16-1123
Citation  Lin JJ, et al. (2017) Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 7(2):137-155
abstractText  Anaplastic lymphoma kinase (ALK) is a validated molecular target in several ALK-rearranged malignancies, including non-small cell lung cancer. However, the clinical benefit of targeting ALK using tyrosine kinase inhibitors (TKI) is almost universally limited by the emergence of drug resistance. Diverse mechanisms of resistance to ALK TKIs have now been discovered, and these basic mechanisms are informing the development of novel therapeutic strategies to overcome resistance in the clinic. In this review, we summarize the current successes and challenges of targeting ALK. SIGNIFICANCE: Effective long-term treatment of ALK-rearranged cancers requires a mechanistic understanding of resistance to ALK TKIs so that rational therapies can be selected to combat resistance. This review underscores the importance of serial biopsies in capturing the dynamic therapeutic vulnerabilities within a patient's tumor and offers a perspective into the complexity of on-target and off-target ALK TKI resistance mechanisms. Therapeutic strategies that can successfully overcome, and potentially prevent, these resistance mechanisms will have the greatest impact on patient outcome. Cancer Discov; 7(2); 137-55. (c)2017 AACR.
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