Targeting FGFR Attenuates Tumor Growth in an Anal Squamous Cell Carcinoma Patient Derived Xenograft Model

Molecular Carcinogenesis, Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

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

Язык: Английский

Discovery of INCB126503 as a Potent and Selective FGFR2/3 Inhibitor

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер unknown

Опубликована: Май 17, 2025

Язык: Английский