Fig. 6

The therapeutic effect of anlotinib on the BRAFv600e⁻ PCP mouse model and BRAFv600e⁻ PCP patients. A: Spatial transcriptome sequencing data from the calcifaied PCP patient 1, who carried the BRAFv600e mutation, indicated that the fibroblasts (cluster 5) specifically expressed PDGFR. A1: Fibroblasts (Cluster 5) surrounding PCP cells on a spatial map. A2-A4: PDGFR is the most specifically expressed gene in fibroblasts (cluster 5). B: In tumor tissues from BRAFv600e⁺ PCP patients, PDGFR was highly expressed in the tumor mesenchyme. C: In tumor tissues from BRAFv600e⁻ PCP patients, PDGFR was also abundantly expressed in the tumor mesenchyme, where the fibroblasts were located. D: Imaging changes caused by anlotinib (a PDGFR inhibitor) therapy in BRAFv600e⁻ PCP mice. At the 1th day of therapy, mouse MRI showed solid component of the tumor (yellow arrow). At the 7th day of therapy, the solid component of the tumor had significantly shrunk (yellow arrow) (n = 6). The tumors in the brains of the control mice (without any treatment) continued to grow, with the yellow arrow indicating the tumor (n = 3). E: Histological changes caused by anlotinib therapy in BRAFv600e⁻ PCP mice. At the 7th day of therapy, the squamous epithelium had completely disappeared, leaving scar tissue (n = 6); however, the squamous epithelium was still intact in the tumor tissue of the control mice (n = 3). F: Detailed presentation of two patients with BRAFv600e⁻ PCP from the early stage of the disease to clinical cure. 1–5: Calcified PCP Patient 2 (male, 21 years old), negative for the BRAFv600e mutation. 1: The yellow arrow in the preoperative CT image indicates tumor calcification. 2: The yellow dotted box in the preoperative MR-T1WI enhancement image indicates the tumor. 3: The patient underwent tumor resection surgery, and the tumor recurred 1 year after surgery (indicated by the yellow dotted box). 4: After tumor recurrence, the patient received oral treatment with anlotinib capsules, and the tumor essentially disappeared after 3 months of treatment, leaving the pituitary intact (indicated by the yellow dotted box). 5: After 24 months of follow-up, there was no tumor recurrence (yellow dotted box). 6–10: Calcified PCP Patient 4 (female, 18 years old), negative for the BRAFv600e mutation. 6: The yellow arrow in the preoperative CT image indicates tumor calcification. 7: The yellow dotted box in the preoperative MR-T1WI enhancement image indicates the tumor. 8: The patient underwent tumor resection surgery, and the tumor recurred 14 months after surgery (indicated by the yellow dotted box). 9: After tumor recurrence, the patient received oral treatment with anlotinib capsules, and the tumor essentially disappeared after 3 months of treatment, leaving the pituitary intact (indicated by the yellow dotted box). 10: After 24 months of follow-up, there was no tumor recurrence (yellow dotted box)