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Review
. 2022 Sep;77(3):411-418.
doi: 10.1007/s12020-022-03074-z. Epub 2022 May 18.

FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma

Mariangela Tamburello  1   2 , Barbara Altieri  1 , Iuliu Sbiera  1 , Sandra Sigala  2 , Alfredo Berruti  3 , Martin Fassnacht  1   4 , Silviu Sbiera  5
Affiliations
Review

FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma

Mariangela Tamburello et al. Endocrine. 2022 Sep.

Abstract

FGF/FGFR signaling regulates embryogenesis, angiogenesis, tissue homeostasis and wound repair by modulating proliferation, differentiation, survival, migration and metabolism of target cells. Understandably, compelling evidence for deregulated FGF signaling in the development and progression of different types of tumors continue to emerge and FGFR inhibitors arise as potential targeted therapeutic agents, particularly in tumors harboring aberrant FGFR signaling. There is first evidence of a dual role of the FGF/FGFR system in both organogenesis and tumorigenesis, of which this review aims to provide an overview. FGF-1 and FGF-2 are expressed in the adrenal cortex and are the most powerful mitogens for adrenocortical cells. Physiologically, they are involved in development and maintenance of the adrenal gland and bind to a family of four tyrosine kinase receptors, among which FGFR1 and FGFR4 are the most strongly expressed in the adrenal cortex. The repeatedly proven overexpression of these two FGFRs also in adrenocortical cancer is thus likely a sign of their participation in proliferation and vascularization, though the exact downstream mechanisms are not yet elucidated. Thus, FGFRs potentially offer novel therapeutic targets also for adrenocortical carcinoma, a type of cancer resistant to conventional antimitotic agents.

Keywords: Adrenocortical development; Adrenocortical tumors; FGF-pathway; FGFR; FGFR-inhibitors.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Changes in FGF to receptor binding specificity depending on tissue-specific isoform splicing for FGFR 1-3
See this image and copyright information in PMC

Comment in

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