Targeting the Tumor Microenvironment: FAPi Theranostics Offers Hope in “Untreatable” Thyroid Cancer
Original Article: Long-Term Outcomes in Radioiodine-Resistant Follicular Cell-Derived Thyroid Cancers Treated with [¹⁷⁷Lu]Lu-DOTAGA.FAPi Dimer Therapy
What are the key takeaways of this article?
Radioiodine-refractory thyroid cancer leaves patients with scant systemic options. Scientists turned to the tumor’s stroma, targeting fibroblast-activation protein (FAP) with a ¹⁷⁷Lu-labeled DOTAGA dimer. Seventy-three heavily pre-treated patients received a median 22 GBq over up to nine cycles. The treatment was outpatient and well-tolerated (≤ 5 % grade ≥ 3 hematologic toxicity, zero grade 3 renal/hepatic events).
Median progression-free survival stretched to 29 months and overall survival to 32 months which are remarkable numbers in this hard-to-treat cohort and roughly double historical controls. Response correlated with baseline FAPi-PET uptake, hinting at a theranostic biomarker.
The retrospective design demands controlled trials, yet the data ignite interest in combination regimens (α-emitters, immunotherapy) and in expanding FAP-targeted radioligands to other solid tumors. If validated, FAPi therapy could shift the paradigm from cell-directed to microenvironment-directed oncology.
Publication Date: February 2025
Reference: Giannoula E, Müller L, Rühlmann M, et al. Thyroid. 2025;35(2):250-261. doi:10.1089/thy.2024.0229
Summary By: Tauqeer