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头颈部癌症中 FGFR 信号的治疗靶向。

Therapeutic Targeting of FGFR Signaling in Head and Neck Cancer.

机构信息

From the Departments of Pharmacology.

出版信息

Cancer J. 2022;28(5):354-362. doi: 10.1097/PPO.0000000000000615.


DOI:10.1097/PPO.0000000000000615
PMID:36165723
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9523489/
Abstract

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most prevalent cancer worldwide, with an annual incidence of 600,000 new cases. Despite advances in surgery, chemotherapy, and radiotherapy, the overall survival for HNSCC patients has not been significantly improved over the past several decades. Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) genomic alterations are frequently detected in HNSCC, including amplification, activating mutation, and chromosomal rearrangement. Among them, FGFR1 amplification, FGF amplifications, and FGFR3 mutations are the most prevalent. In addition, FGF/FGFR expression has also been observed in most HNSCCs. However, the prognostic value of FGF/FGFR aberrations remains unclear, especially for gene amplification and overexpression. Nonetheless, FGF/FGFR has been a promising target for HNSCC treatment, and recent preclinical studies demonstrate the potential of the combination treatment regimens involving FGFR inhibitors on HNSCC. Therefore, there are a number of FGFR inhibitors currently in clinical trials for the treatment of head and neck cancers.

摘要

头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症,每年新发病例约 60 万例。尽管在手术、化疗和放疗方面取得了进展,但在过去几十年中,HNSCC 患者的总体生存率并未得到显著改善。在 HNSCC 中经常检测到成纤维细胞生长因子(FGF)/成纤维细胞生长因子受体(FGFR)基因改变,包括扩增、激活突变和染色体重排。其中,FGFR1 扩增、FGF 扩增和 FGFR3 突变最为常见。此外,大多数 HNSCC 中也观察到 FGF/FGFR 的表达。然而,FGF/FGFR 异常的预后价值尚不清楚,尤其是对于基因扩增和过表达。尽管如此,FGF/FGFR 一直是 HNSCC 治疗的一个有前途的靶点,最近的临床前研究表明,FGFR 抑制剂联合治疗方案对 HNSCC 具有潜在的治疗作用。因此,目前有许多 FGFR 抑制剂正在进行头颈部癌症的临床试验。

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本文引用的文献

[1]
Germline Variants in Angiogenesis-Related Genes Contribute to Clinical Outcome in Head and Neck Squamous Cell Carcinoma.

Cancers (Basel). 2022-4-6

[2]
Precision drugging of the MAPK pathway in head and neck cancer.

NPJ Genom Med. 2022-3-16

[3]
Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.

Head Neck. 2022-5

[4]
FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies.

Ann Oncol. 2022-5

[5]
Immunomodulation via FGFR inhibition augments FGFR1 targeting T-cell based antitumor immunotherapy for head and neck squamous cell carcinoma.

Oncoimmunology. 2022

[6]
Fibroblast growth factor (FGF), FGF receptor (FGFR), and cyclin D1 (CCND1) DNA methylation in head and neck squamous cell carcinomas is associated with transcriptional activity, gene amplification, human papillomavirus (HPV) status, and sensitivity to tyrosine kinase inhibitors.

Clin Epigenetics. 2021-12-21

[7]
AZD4547 targets the FGFR/Akt/SOX2 axis to overcome paclitaxel resistance in head and neck cancer.

Cell Oncol (Dordr). 2022-2

[8]
Targeted molecular characterization of external auditory canal squamous cell carcinomas.

Laryngoscope Investig Otolaryngol. 2021-9-13

[9]
Targeted Therapy With PI3K and FGFR Inhibitors on Human Papillomavirus Positive and Negative Tonsillar and Base of Tongue Cancer Lines With and Without Corresponding Mutations.

Front Oncol. 2021-5-11

[10]
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

CA Cancer J Clin. 2021-5

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