Drug resistance of ALK mutants

Stable Identifier
Homo sapiens
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Aberrant ALK activity arises through fusions, point mutations, overexpression or amplifications and has been shown to be an oncogenic driver in a number of cancers including anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), inflammatory myofibroblastic tumors (IMTs) neuroblastomas and more (reviewed in Della Corte et al, 2018; Lin et al, 2017). As a result, ALK is a promising therapeutic target for inhibition with tyrosine kinase inhibitors. Crizotinib, ceritinib, brigatinib, alectinib and lorlatinib are all approved for the treatment of ALK-driven cancers, however resistance commonly develops either as a result of accumulating secondary mutations, or through activation of bypass pathways that remove the dependence on ALK signaling (reviewed in Della Corte et al, 2017; Roskoski, 2013; Lin et al, 2017).

Literature References
PubMed ID Title Journal Year
29455642 Role and targeting of anaplastic lymphoma kinase in cancer

Troiani, T, Viscardi, G, Morgillo, F, Fasano, M, Martinelli, E, Ciardiello, F, Della Corte, CM, Di Liello, R

Mol. Cancer 2018
23201355 Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition

Roskoski, R

Pharmacol. Res. 2013
28122866 Targeting ALK: Precision Medicine Takes on Drug Resistance

Shaw, AT, Riely, GJ, Lin, JJ

Cancer Discov 2017
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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