CD44v6 expression in non-anaplastic thyroid carcinoma: characterization of candidates for targeted therapy.

Stenman A, Nilsson JN, Condello V, L Mortensen AC, Nestor M, Zedenius J, Juhlin CC

Thyroid Res 18 (1) 47 [2025-10-03; online 2025-10-03]

CD44v6 is a membranous antigen upregulated in solid tumors and a promising molecular radiotherapy target, especially in anaplastic thyroid carcinoma (ATC). A Phase 1 trial recently launched to evaluate the lutetium-labeled anti-CD44v6 antibody [1⁷⁷Lu]Lu-DOTA-AKIR001 in CD44v6-positive solid tumors. Given limited data in non-ATC, we assessed CD44v6 immunoreactivity in tumors that may progress to a radioiodine-refractory state. An exploratory cohort of 33 tumors (30 papillary thyroid carcinomas [PTCs], 3 poorly differentiated thyroid carcinomas [PDTCs]) was screened using the VFF-7 antibody, supported by detailed iodine concentration, genetic, and RNA sequencing data. A validation cohort of 40 oncocytic thyroid carcinomas (OTCs), 28 additional PDTCs, and one differentiated high-grade thyroid carcinoma was also screened using two antibody clones, VFF-7 and VFF-18. In the exploratory cohort, 10 of 33 tumors (30%) showed focal or diffuse CD44v6 expression, while the rest were negative. Among OTCs in the validation cohort, 15 of 40 (38%) were partially or diffusely positive, and in PDTCs, 14 of 28 (50%) showed focal or diffuse staining. The VFF-7 and VFF-18 clones produced similar patterns. Substantial subsets of non-ATCs express CD44v6, indicating that some patients may be candidates for [1⁷⁷Lu]Lu-DOTA-AKIR001 radiotherapy, particularly when conventional treatments are exhausted.

PubMed 41039489

DOI 10.1186/s13044-025-00266-3

Crossref 10.1186/s13044-025-00266-3

pmc: PMC12492884
pii: 10.1186/s13044-025-00266-3