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- W4387172152 abstract "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." @default.
- W4387172152 created "2023-09-30" @default.
- W4387172152 creator A5053481267 @default.
- W4387172152 creator A5071742593 @default.
- W4387172152 creator A5071800834 @default.
- W4387172152 creator A5081736870 @default.
- W4387172152 creator A5083509294 @default.
- W4387172152 creator A5086626483 @default.
- W4387172152 creator A5090983842 @default.
- W4387172152 date "2023-09-29" @default.
- W4387172152 modified "2023-10-18" @default.
- W4387172152 title "ALK fusions in the pan-cancer setting: another tumor-agnostic target?" @default.
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