Rationale for targeting fibroblast growth factor receptor signaling in breast cancer.
Rationale for targeting fibroblast growth factor receptor signaling in breast cancer.
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DOI：
10.1007/s10549-015-3301-y
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发表时间：
2015-02
影响因子：
3.8
通讯作者：
Cortes, Javier
中科院分区：
文献类型：
--
作者：
Andre, Fabrice;Cortes, Javier
关键词：
成纤维细胞生长因子受体（FGFR）信号转导参与多种生物学过程，包括胚胎发育和成体组织稳态期间的细胞增殖、存活、分化、迁移和凋亡。鉴于其在关键信号传导途径活化中的作用，异常FGFR信号传导已涉及多种癌症类型。对PubMed和会议摘要进行了全面检索，以确定乳腺癌中FGFR通路组分的报告。在乳腺癌中，已检测到FGFR 1和FGFR 4基因扩增以及FGFR 2和FGFR 4中的单核苷酸多态性。通常，这些FGFR畸变和基因扩增导致FGFR信号传导增加，并与预后不良和对乳腺癌治疗的耐药性有关。在这里，我们回顾FGFR信号的作用和FGFR基因扩增/畸变对乳腺肿瘤的影响。此外，我们总结了FGFR靶向治疗乳腺癌的最新临床前和临床数据。最后，我们强调了正在进行的FGFR靶向药物dovitinib，AZD 4547，lucitanib，BGJ 398和JNJ-42756493的临床试验，这些药物被选择用于FGFR通路扩增的乳腺癌患者。异常的FGFR途径扩增可能会导致一些乳腺癌。临床上正在探索FGFR信号传导的抑制，这些试验的数据可能会提高我们选择对这些治疗反应最好的患者的能力。
Fibroblast growth factor receptor (FGFR) signaling is involved in multiple biological processes, including cell proliferation, survival, differentiation, migration, and apoptosis during embryonic development and adult tissue homeostasis. Given its role in the activation of critical signaling pathways, aberrant FGFR signaling has been implicated in multiple cancer types. A comprehensive search of PubMed and congress abstracts was conducted to identify reports on FGFR pathway components in breast cancer. In breast cancers, FGFR1 and FGFR4 gene amplification and single nucleotide polymorphisms in FGFR2 and FGFR4 have been detected. Commonly, these FGFR aberrations and gene amplifications lead to increased FGFR signaling and have been linked with poor prognosis and resistance to breast cancer treatments. Here, we review the role of FGFR signaling and the impact of FGFR genetic amplifications/aberrations on breast tumors. In addition, we summarize the most recent preclinical and clinical data on FGFR-targeted therapies in breast cancer. Finally, we highlight the ongoing clinical trials of the FGFR-targeted agents dovitinib, AZD4547, lucitanib, BGJ398, and JNJ-42756493, which are selected for patients with FGFR pathway-amplified breast cancer. Aberrant FGFR pathway amplification may drive some breast cancers. Inhibition of FGFR signaling is being explored in the clinic, and data from these trials may refine our ability to select patients who would best respond to these treatments.
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影响因子：
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作者：
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