ALK fusions in the pan-cancer setting: another tumor-agnostic target? NPJ Precis Oncol 2023 Sep 29;7(1):101
Date
09/29/2023Pubmed ID
37773318Pubmed Central ID
PMC10542332DOI
10.1038/s41698-023-00449-xScopus ID
2-s2.0-85173930134 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Anaplastic lymphoma kinase (ALK) alterations (activating mutations, amplifications, and fusions/rearrangements) occur in ~3.3% of cancers. ALK fusions/rearrangements are discerned in >50% of inflammatory myofibroblastic tumors (IMTs) and anaplastic large cell lymphomas (ALCLs), but only in ~0.2% of other cancers outside of non-small cell lung cancer (NSCLC), a rate that may be below the viability threshold of even large-scale treatment trials. Five ALK inhibitors -alectinib, brigatinib, ceritinb, crizotinib, and lorlatinib-are FDA approved for ALK-aberrant NSCLCs, and crizotinib is also approved for ALK-aberrant IMTs and ALCL, including in children. Herein, we review the pharmacologic tractability of ALK alterations, focusing beyond NSCLC. Importantly, the hallmark of approved indications is the presence of ALK fusions/rearrangements, and response rates of ~50-85%. Moreover, there are numerous reports of ALK inhibitor activity in multiple solid and hematologic tumors (e.g., histiocytosis, leiomyosarcoma, lymphoma, myeloma, and colorectal, neuroendocrine, ovarian, pancreatic, renal, and thyroid cancer) bearing ALK fusions/rearrangements. Many reports used crizotinib or alectinib, but each of the approved ALK inhibitors have shown activity. ALK inhibitor activity is also seen in neuroblastoma, which bear ALK mutations (rather than fusions/rearrangements), but response rates are lower (~10-20%). Current data suggests that ALK inhibitors have tissue-agnostic activity in neoplasms bearing ALK fusions/rearrangements.
Author List
Shreenivas A, Janku F, Gouda MA, Chen HZ, George B, Kato S, Kurzrock RAuthors
Hui-Zi Chen MD, PhD Assistant Professor in the Medicine department at Medical College of WisconsinBen George MD Professor in the Medicine department at Medical College of Wisconsin
