Fibroblast Growth Factor Receptor 2, or FGFR2, is a protein located on the surface of cells throughout the body. It functions as a receiver, picking up signals from outside the cell. These signals, called fibroblast growth factors (FGFs), bind to FGFR2, prompting the receptor to activate internal cellular processes. This interaction is a fundamental part of cell communication, allowing cells to respond to their environment and coordinate various biological activities.
Understanding FGFR2’s Normal Functions
FGFR2 plays a key role in normal physiological processes, guiding cellular development and maintenance. It is deeply involved in embryonic development, guiding the formation of bones and other tissues, including mammary glands and breast tissue maintenance.
The receptor also directs cell growth and differentiation, where cells specialize into different types. Beyond development, FGFR2 contributes to tissue homeostasis, ensuring tissue stability and correct function. Its signaling pathway also has a role in new blood vessel formation (angiogenesis) and wound healing.
FGFR2 and Developmental Disorders
Mutations in the FGFR2 gene can disrupt its normal function, leading to various congenital developmental disorders. These conditions are present from birth and primarily affect skull and face development. A common outcome is craniosynostosis, where skull bones fuse prematurely before brain growth is complete.
Examples of these genetic syndromes include Apert syndrome, characterized by severe craniosynostosis, often with fused fingers and toes. Crouzon syndrome also involves craniosynostosis, causing facial features like widely spaced eyes and a prominent jaw. Pfeiffer syndrome, also linked to FGFR2 mutations, presents with similar skull abnormalities, broad thumbs, and broad big toes. These features arise because mutated FGFR2 sends incorrect signals, disrupting bone development during gestation.
FGFR2’s Role in Cancer
Beyond developmental conditions, alterations in FGFR2 also contribute to the development and progression of various cancers. Unlike inherited mutations in developmental disorders, these FGFR2 changes in cancer are acquired during a person’s lifetime. These alterations can include gene amplification, where many copies are made, or gene fusions, where parts combine with other genes.
These changes lead to FGFR2 overactivity, causing uncontrolled cell growth and survival. For instance, FGFR2 gene fusions are frequently found in cholangiocarcinoma, a type of bile duct cancer, where they play a significant role in tumor development and progression. FGFR2 amplification is also observed in some gastric cancers, though it is less common, occurring in about 5% of cases. Additionally, FGFR2 has a role in breast cancer, with some studies suggesting that increased FGFR2 gene expression might contribute to risk.
Therapeutic Approaches Targeting FGFR2
Understanding the abnormal activity of FGFR2 in diseases like cancer has paved the way for the development of targeted therapies. These therapies are designed to specifically block the overactive FGFR2 signaling, aiming to stop or slow the uncontrolled cell growth seen in certain cancers. Instead of broadly affecting all rapidly dividing cells like traditional chemotherapy, these drugs are more precise.
The goal of these targeted approaches is to interfere with the specific molecular mechanisms driven by abnormal FGFR2, such as blocking the activation of pathways like Ras-MAPK and PI3K-AKT that promote cell survival and proliferation. While these therapies offer a promising strategy, challenges such as the development of drug resistance can arise as cancer cells may find alternative signaling pathways to bypass the inhibition. Ongoing research continues to explore combination therapies that target FGFR2 alongside these alternative pathways to enhance treatment effectiveness.