Insights of fibroblast growth factor receptor 3 aberrations in pan-cancer and their roles in potential clinical treatment

Li, Juanni; Hu, Kuan; Huang, Jinzhou; Zhou, Lei; Yan, Yuanliang; Xu, Zhijie

doi:10.18632/aging.203175

Cited by 7 publications

(5 citation statements)

References 64 publications

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“…Recent reports have investigated the use of erdafitinib in other tumors expressing FGFR mutations, including gliomas. 45 FGFR-1 alteration is a common mutation associated with RGNT, as was found in our patient. To the best of our knowledge, this is the first report in the literature of erdafitinib used to treat RGNT.…”

Section: Discussionsupporting

confidence: 80%

Diffusely invasive supratentorial rosette-forming glioneuronal tumor: illustrative case

Owusu-Adjei,

Mietus,

Lim

et al. 2023

Journal of Neurosurgery: Case Lessons

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BACKGROUND Rosette-forming glioneuronal tumors (RGNTs) are rare tumors composed of mixed glial and neurocytic components. Most lesions are confined to the posterior fossa, especially in the region of the fourth ventricle, in young adults. In few instances, diffuse involvement of the supratentorial region is identified, thereby creating significant challenges in diagnosis, surgical intervention, and prognostication. OBSERVATIONS The authors present a 23-year-old female with chronic headaches, papilledema, and hydrocephalus who underwent radiographic evaluation revealing obstructive hydrocephalus and diffuse supratentorial enhancing and nonenhancing cystic and nodular lesions. The patient underwent a right frontal craniotomy and septostomy. An exophytic nonenhancing right frontal horn lesion was resected, and an enhancing third-ventricular lesion was biopsied. Final pathology of both of the lesions sampled was consistent with RGNT. Next-generation sequencing demonstrated tumor alterations in the FGFR-1 and PIK3CA genes. Targeted therapy with the FGFR inhibitor erdafitinib demonstrated a partial remission. LESSONS Diffuse supratentorial spread of RGNT is an extremely rare presentation of an already uncommon pathology. In some cases, gross-total resection may not be feasible. Goals of surgery include acquiring tissue for diagnosis, maximizing safe resection, and treating any associated hydrocephalus. FGFR inhibitors may be of benefit in cases of disease progression.

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Section: Discussionsupporting

confidence: 80%

Diffusely invasive supratentorial rosette-forming glioneuronal tumor: illustrative case

Owusu-Adjei,

Mietus,

Lim

et al. 2023

Journal of Neurosurgery: Case Lessons

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“…However, FGFR3 gene alterations are rarely observed in patients with NSCLC. FGFR3 hotspot mutations, R248C and S249C, and FGFR3 fusions are found in 0.1% and 0.14% of NSCLC cases, respectively (24). In pulmonary LELC, the actionable alteration FGFR3 (FGFR3 R248C and FGFR3-TACC3 fusion) was 3.39% (2/59), as detected by Chau et al (25).…”

Section: Discussionmentioning

confidence: 83%

Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification

et al. 2021

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BackgroundPrimary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient’s resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment.Case PresentationA 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months.ConclusionPulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

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“…The analysis of data obtained from The Cancer Genome Atlas (TCGA) demonstrated that the presence of targetable mutations in the FGFR 3 gene was predominantly observed in bladder cancer. Specifically, the mutations S249C, Y373C, G370C, and R248C were identified as hotspot mutations, which can be effectively targeted by the FDA-approved drug erdafitinib [ 53 ]. Additionally, the occurrence of FGFR 3 S249C mutation was less frequent in upper tract urothelial carcinoma patients compared to bladder cancer patients (37.5% vs. 59.3%) [ 54 ].…”

Section: Prevalence and Diversity Of Fgfr Abnormal...mentioning

confidence: 99%

Targeting FGFR for cancer therapy

Zhang,

Yue,

Leng

et al. 2024

J Hematol Oncol

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The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current state of clinical research in this field. Then, we highlight four drugs that have been approved for marketing by the FDA, offering insights into their molecular mechanisms and clinical achievements. Our discussion encompasses the intricate landscape of FGFR-driven tumorigenesis, current techniques for pinpointing FGFR anomalies, and clinical experiences with FGFR inhibitor regimens. Furthermore, we discuss the inherent challenges of targeting the FGFR pathway, encompassing resistance mechanisms such as activation by gatekeeper mutations, alternative pathways, and potential adverse reactions. By synthesizing the current evidence, we underscore the potential of FGFR-centric therapies to enhance patient prognosis, while emphasizing the imperative need for continued research to surmount resistance and optimize treatment modalities.

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Insights of fibroblast growth factor receptor 3 aberrations in pan-cancer and their roles in potential clinical treatment

Cited by 7 publications

References 64 publications

Diffusely invasive supratentorial rosette-forming glioneuronal tumor: illustrative case

Diffusely invasive supratentorial rosette-forming glioneuronal tumor: illustrative case

Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification

Targeting FGFR for cancer therapy

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