Several mutations in FGFR4 have been identified in 7–8% of rhabdomyosarcomas (RMS), associating with advanced stage and poor survival. The mutations occur in the auto-phosphorylation sites of the receptor (N535K and V550E) and increase the ability to invade and metastasise in both in vitro and in vivo studies. SNPs of FGFR have also been identified in human cancers. Similarly, the germline SNP in FGFR4 at nucleotide 388 correlates with a higher resistance to chemotherapy in patients with breast cancer. In a mammary carcinoma model the FGFR4 G388R mutation was found to promote cancer progression and metastasis. This may be because of impaired degradation compared to the wild type receptor, resulting in sustained signalling. A SNP within intron 2 of FGFR2 is associated with an increased risk of ER+ve breast cancer.
Drug targets for cancer: FGFR4 research reagents
Other vital drug targets for cancer likeFGFR4:
Touat M, Ileana E, Postel-Vinay S, et al. Targeting FGFR signaling in cancer[J]. Clinical Cancer Research, 2015, 21(12): 2684-2694.