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Karl D. Lewis, MD


AACR 2022: FGFR Inhibitor Under Study in UVB-Induced Squamous Cell Carcinoma

By: Lauren Harrison, MS
Posted: Wednesday, April 20, 2022

Topical application of the fibroblast growth factor receptor (FGFR) inhibitor AZD4547 appeared to generate a low systemic absorption prolife, and therefore it may prove to be useful in both treating and preventing ultraviolet B (UVB)-induced cutaneous squamous cell carcinoma, according to Cherie-Ann O. Nathan, MD, of Ochsner LSU Health in Shreveport, Louisiana, and colleagues. They previously found that topical application of AZD4547 led to a reduction in epidermal hyperplasia and hyperproliferation and inhibited UVB-induced tumor incidence and multiplicity. This recent preclinical study was presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 5425).

In this study, mice were administered 400 µg/200 µL of topical AZD4547 and then underwent exposure to UVB rays three times a week for 2 weeks. Their blood was collected at the end of the study and was analyzed for AZD4547 absorption. AZD4547 was extracted using the methanol extraction method before being concentrated. The samples of the compound were then reconstituted in an acetone and water solution and analyzed using chromatography.

High-performance liquid chromatography analysis of the blood samples showed a nonappreciable absorption of AZD4547, with levels of between 108 and 358 nM. This suggests that topical application of AZD4547 does not lead to systemic absorption of the compound. In addition, this allows for the efficacy of the treatment to be restricted to the local skin tissue.

“Based on the efficacy and low systemic absorption profile, AZD4547 could potentially be utilized as a topical agent to both prevent and treat UVB-induced cutaneous squamous cell carcinoma,” the investigators concluded.

Disclosure: The study authors reported no conflicts of interest.

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