FGFR2 in the Development and Progression of Cutaneous Squamous Cell Cancer

Mol Carcinog. 2025 Jan;64(1):5-13. doi: 10.1002/mc.23835. Epub 2024 Oct 28.

Abstract

Cutaneous squamous cell carcinoma (cSCC) is an increasingly common malignancy of the skin and the leading cause of death from skin cancer in adults over the age of 85. Fibroblast growth factor receptor 2 (FGFR2) has been identified as an important effector of signaling pathways that lead to the growth and development of cSCC. In recent years, there have been numerous studies evaluating the role FGFR2 plays in multiple cancers, its contribution to resistance to anticancer therapy, and new drugs that may be used to inhibit FGFR2. This review will provide an overview of our current understanding of FGFR2 and potential mechanisms in which we can target FGFR2 in cSCC. The goals of this review are the following: (1) to highlight our current knowledge of the role of FGFR2 in healthy skin and contrast this with its role in the development of cancer; (2) to further explain the specific molecular mechanisms that FGFR2 uses to promote tumorigenesis; (3) to describe how FGFR2 contributes to more invasive disease; (4) to describe its immunosuppressive effects in skin; and (5) to evaluate its effect on current anticancer therapy and discuss therapies on the horizon to target FGFR2 related malignancy.

Keywords: epithelial−mesenchymal transition; immunosuppression; metastasis; treatment resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Disease Progression*
  • Humans
  • Receptor, Fibroblast Growth Factor, Type 2* / genetics
  • Receptor, Fibroblast Growth Factor, Type 2* / metabolism
  • Signal Transduction
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology

Substances

  • Receptor, Fibroblast Growth Factor, Type 2
  • FGFR2 protein, human