A systematic evaluation of the efficacy and safety of entrectinib in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with limited treatment options and poor responsiveness to conventional chemotherapy. In this study, we found that TrkA expression was markedly elevated in clinical ATC tissues compared with adjacent normal thyroid tissue. Knockdown of NTRK1, which encodes TrkA, reduced cell viability and sensitized ATC cells to paclitaxel. Consistently, the Trk inhibitor entrectinib decreased viability of genetically diverse ATC cell lines with nanomolar IC50 values, and demonstrated synergy with paclitaxel across all tested lines. In vivo, entrectinib significantly delayed tumour progression in two independent xenograft studies, while combination therapy produced the most sustained suppression of tumour growth and the greatest extension of survival. Entrectinib was well tolerated at the administered dose, with no significant changes in body weight and serum biochemical markers. Collectively, these findings identify TrkA as a potential therapeutic target in ATC and support further investigation of entrectinib-based combination strategies to improve ATC treatment outcomes.