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Bladder Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Approximately 15–20% of patients with metastatic urothelial cancer harbor mutations of amplifications in FGFR2 or FGFR3. A molecularly targeted phase II study of the FGFR2/3 inhibitor, erdafitinib, has reported a 40% ORR and median duration of overall survival of 13.8 months in mutation carriers and has now entered phase III testing.128
Oral and craniofacial disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Several specific genetic and clinical types of craniosynostosis exist, which are important to distinguish in genetic counselling. Gorlin's Syndromes of the Head and Neck (see Appendix 1) provides a detailed description. The principal types are listed in Table 17.3. Recognition of the different molecular defects (notably in fibroblast growth factor receptor 2) has been of great importance. All forms except Carpenter syndrome are autosomal dominant, with many cases (almost all in Apert syndrome) due to new mutation.
Clefts and craniofacial
Published in Tor Wo Chiu, Stone’s Plastic Surgery Facts, 2018
Type IIIAnkylosis of elbows but no Kleeblattschädel and mental disability. Types II and III are associated with FGFR2 gene mutations only.
Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer
Published in OncoImmunology, 2021
Siyu Xia, Yun Gu, Haijian Zhang, Yuchao Fei, Yifan Cao, Hanji Fang, Jieti Wang, Chao Lin, Heng Zhang, He Li, Hongyong He, Jiejie Xu, Ruochen Li, Hao Liu, Weijuan Zhang
In recent years, targeted therapies, including Trastuzumab, Ramucirumab, and Bemarituzumab,38,39 have drawn growing attention in the adjuvant treatment of GC. Herein, we inspected the association between APOBEC3B and the corresponding pathways in GC. Known as promising therapeutic targets in gastric cancer, human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) signaling score were both elevated in APOBEC3B-enriched tumors, whereas no association was observed between CLDN18.2 or fibroblast growth factor receptor 2 (FGFR2) and APOBEC3B in GC (Supplementary Figure S6C). Additionally, we also inspected the potential value of APOBEC3B in predicting immunotherapeutic responsiveness to programmed cell death protein 1 (PD-1) blockade in GC. However, no association between immunotherapeutic responsiveness and APOBEC3B was observed in our current study (Figure 4(c)), which might result from the relatively small size of the ICB Cohort.40
Urothelial carcinoma: the development of FGFR inhibitors in combination with immune checkpoint inhibitors
Published in Expert Review of Anticancer Therapy, 2020
Qian Qin, Vaibhav Patel, Matthew D Galsky
FGFR3 alterations are among the most common recurrent molecular alterations in UC [5–8,10,29–32]. Among all cancer types assayed in the large next generation sequencing (NGS) analysis, over 30% of UCs harbored FGFR alterations with a predilection for FGFR3 (i.e., mutations, fusions, or over-expressions) followed by FGFR1 [30]. The majority of FGFR3 alterations are activating mutations, such as S249 C (most common) and R248 C in the extracellular domain, Y375 C and G372 C in the transmembrane domain, and K652E in the kinase domain [5,7,29,30]. Greater than 70% of benign lesions/non-muscle invasive bladder cancer (NMIBC) and up to 20% of muscle invasive bladder cancer (MIBC) possess FGFR3 mutations [5–15]. Though less common, overexpression of FGFR3, alternative splicing of FGFR3, and FGFR1 aberrations can occur and may play a role in the pathogenesis of UC [5,12,33–35]. Conversely, FGFR2 has been associated with context-dependent, anti-proliferative signaling and is often downregulated on bladder cancer progression [36].
Does CETP rs5882, rs708272, SIRT1 rs12778366, FGFR2 rs2981582, STAT3 rs744166, VEGFA rs833068, IL6 rs1800795 polymorphisms play a role in optic neuritis development?
Published in Ophthalmic Genetics, 2019
Greta Gedvilaite, Alvita Vilkeviciute, Loresa Kriauciuniene, Virginija Asmoniene, Rasa Liutkeviciene
There are also studies that demonstrate the association of genetic polymorphisms of fibroblast growth factor receptor 2 (FGFR2) with cancerous cells development. The fibroblast growth factor plays an important role in many important processes like formation of blood vessels, regeneration and wound healing, cell growth, and embryonic development. The FGFR2 gene is grouped into two variants, FGFR2 IIIb, and FGFR2 IIIc, and the protein encoded by this gene is a member of the fibroblast growth factor receptor family, where the amino acid sequence is highly conserved between the members. The protein spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This positioning allows the FGFR2 protein to interact with specific growth factors outside the cell and to receive signals that help the cell respond to its environment (24). When growth factors attach to the FGFR2 protein, the receptor triggers a cascade of chemical reactions inside the cell that instruct the cell to undergo certain changes. Genetic changes in the FGFR2 protein lead to unbalanced functions of cells and optic nerve damage by reinless cell growth without a proper apoptosis system. Common variant rs2981582 in the FGFR2 intron was associated with several malignant tumors, such as breast and prostate cancer, promoting their invasiveness and angiogenesis (25–27).