LAUSR

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence and limited treatment options. To identify actionable therapeutic targets, we developed a patient‐derived xenograft (PDX) model using a metastatic ASCC sample and performed single‐cell RNA sequencing. Our analysis confirmed previously reported genetic mutations highly expressed in the sample, along with copy number alterations, and revealed epithelial cancer cell heterogeneity. Notably, epithelial cells exhibited a low hybrid epithelial‐mesenchymal transition (hEMT) signature compared to stromal cells. Among epithelial subpopulations, the most abundant cluster displayed high expression of FGFR1‐2 and FGF ligands. Treatment with AZD4547, an FGFR1‐3 inhibitor, resulted in a significant reduction in tumor volume over time (p = 0.0036). Immunohistochemistry staining for proliferative Ki67 and cleaved caspase 3 suggested ongoing proliferation in residual cells. Fourier‐transform infrared (FTIR) spectroscopy of post‐treatment residual tumors revealed significant differences in the Amide I and Amide II regions between AZD4547‐treated and control groups. These findings demonstrate that FGFR inhibition effectively attenuates ASCC tumor growth and highlights the promise of precision medicine in managing this rare cancer.