Incidence of FGFR-TACC gene fusions in Chinese non-small cell lung cancer (NSCLC): A multicenter study.

Xu, C.; Wang, Wen xian; Zhang, Qu-Xia; Chen, Yu; Fang, Yong; Wang, Hong; Zhu, You‐cai; Zhuang, Wei; Huang, Yun-jian; Zhang, Yinbin; Wang, Liping; Chen, Mei‐Fang; Yang, Dongyong; Cai, Shangli; Fang, M.; Chen, Gang; Lv, Tangfeng; Song, Yong

doi:10.1200/jco.2019.37.15_suppl.e13001

Cited by 2 publications

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“…across multiple solid tumors, in 1/80 TNBC tumors and in vitro studies indicate this fusion protein is a targetable driver in TNBC (34). FGFR2-TACC2 that has been described in glioblastoma (39), NSCLC (40) and cervical cancer (41), was first identified in breast cancer in our study. Table 2 also summarizes other previously reported RTK gene fusions in breast cancer that were not detected in our cohort.…”

Section: Discussionmentioning

confidence: 56%

Profiling Receptor Tyrosine Kinase Fusions in Chinese Breast Cancers

Tao

Liu

et al. 2021

Front. Oncol.

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BackgroundReceptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins that are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. This study aims to characterize RTK fusions in Chinese breast cancer patients.MethodsAn in-house DNA sequencing database of 1440 Chinese breast cancer patients with a capture-based panel (520 gene or 108 gene-panel) was thoroughly reviewed. A total of 2,229 samples including 1,045 tissues and 1,184 plasmas were analyzed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained. Concomitant mutations were also analyzed and tumor mutational burden (TMB) was calculated. Patients’ clinical characteristics were retrieved from case records.ResultsA total of 30 RTK fusion events were identified from 27 breast cancer patients with a prevalence of 1.875%%. FGFR2 fusions were seen the most commonly (n=7), followed by RET (n=5), ROS1 (n=3), NTRK3 (n=3), BRAF (n=2), and NTRK1 (n=2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. A total of 27 unique resultant fusion proteins (22 with a novel partner) were discovered including 19 intrachromosomal rearrangements and 8 interchromosomal ones. Twenty-one fusions had the tyrosine kinase domain in-frame fused with a partner gene and six were juxtaposed with an intergenic space. Among the 27 fusions, FGFR2-WDR11 (E17: intergenic) (n=3) and ETV6-NTRK3 (E5:E15) (n=2) occurred recurrently. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r=-0.48, P=0.017). Patients with TMB < 8 (Mutations/Mb) displayed a higher fusion abundance than those with TMB ≥ 8 (Mutations/Mb) (P=0.025). Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (P=0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (P=0.019).ConclusionThis is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation who may benefit from RTK fusion inhibitors.

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Section: Discussionmentioning

confidence: 56%

Profiling Receptor Tyrosine Kinase Fusions in Chinese Breast Cancers

Tao

Liu

et al. 2021

Front. Oncol.

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“…The FGFR 1- TACC 1 fusion is detected in glioblastoma and SqCC. This fusion is associated with the hyperactivation of FGFR1, which promotes cellular proliferation and inhibits apoptosis [ 58 ]. Additionally, it might augment FGFR1 signaling either by intensifying its tyrosine kinase activity or by modulating its intracellular positioning [ 59 ].…”

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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Incidence of FGFR-TACC gene fusions in Chinese non-small cell lung cancer (NSCLC): A multicenter study.

Cited by 2 publications

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Profiling Receptor Tyrosine Kinase Fusions in Chinese Breast Cancers

Profiling Receptor Tyrosine Kinase Fusions in Chinese Breast Cancers

Targeting FGFR for cancer therapy

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