Combined BRAF and PIM1 inhibitory therapy for papillary thyroid carcinoma based on BRAFV600E regulation of PIM1: Synergistic effect and metabolic mechanisms.

ABSTRACT: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics

SUBMITTER: Xu Q 

PROVIDER: S-EPMC11007432 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature