Targeting FGFR in Squamous Cell Carcinoma of the Lung

Overview

Journal Target Oncol

Specialty Oncology

Date 2017 Jul 8

PMID 28685321

Citations 15

Authors

Neda Hashemi-Sadraei

Nasser Hanna

Affiliations

Soon will be listed here.

Abstract

Unlike for adenocarcinomas of the lung, no molecular targeted therapies have yet been developed for squamous cell lung cancers, because targetable oncogenic aberrations are scarce in this tumor type. Recent discoveries have established that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in cancer development by supporting tumor angiogenesis and cancer cell proliferation via different mechanisms. Through comprehensive genomic studies, aberrations in the FGF pathway have been identified in various tumor types, including squamous cell lung cancer, making FGF receptor (FGFR) a potentially druggable target in this malignancy. Several multi-targeted tyrosine kinase inhibitors include FGFR in their target spectrum and a number of these compounds have been approved for clinical use in different cancers. Novel agents selectively targeting FGFRs have been developed and are currently under investigation in clinical trials, showing promising results. This article reviews FGFR aberrations and the clinical data involving selective and multikinase FGFR inhibitors in squamous cell lung cancer.

Citing Articles

Case report: a case of lung squamous cell carcinoma with a novel FGFR3-IER5L fusion mutation responding to anlotinib.

Chen X, Zhao W, Yu H, Wang S, Wang C, Song Y Front Oncol. 2024; 14:1391349.

PMID: 39421453 PMC: 11484447. DOI: 10.3389/fonc.2024.1391349.

STAT3 inhibitor Stattic Exhibits the Synergistic Effect with FGFRs Inhibitor Erdafitinib in FGFR1-positive Lung Squamous Cell Carcinoma.

Zhong H, Wang L, Zhu X, Li S, Li X, Ding C J Cancer. 2024; 15(16):5415-5424.

PMID: 39247610 PMC: 11375536. DOI: 10.7150/jca.97477.

FGFR1-4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer.

Moes-Sosnowska J, Skupinska M, Lechowicz U, Szczepulska-Wojcik E, Skronska P, Rozy A Int J Mol Sci. 2022; 23(18).

PMID: 36142417 PMC: 9505002. DOI: 10.3390/ijms231810506.

Fibroblast Growth Factor Receptor 1-4 Genetic Aberrations as Clinically Relevant Biomarkers in Squamous Cell Lung Cancer.

Moes-Sosnowska J, Chorostowska-Wynimko J Front Oncol. 2022; 12:780650.

PMID: 35402233 PMC: 8991910. DOI: 10.3389/fonc.2022.780650.

Novel long noncoding RNA (lncRNA) panel as biomarkers for prognosis in lung squamous cell carcinoma via competitive endogenous RNA (ceRNA) network analysis.

Zhang T, Deng L, Ji Y, Cheng G, Su D, Qiu B Transl Cancer Res. 2022; 10(1):393-405.

PMID: 35116269 PMC: 8799182. DOI: 10.21037/tcr-20-2410.

References

Tiseo M, Gelsomino F, Alfieri R, Cavazzoni A, Bozzetti C, De Giorgi A . FGFR as potential target in the treatment of squamous non small cell lung cancer. Cancer Treat Rev. 2015; 41(6):527-39. DOI: 10.1016/j.ctrv.2015.04.011. View

Sleeman M, Fraser J, McDonald M, Yuan S, White D, Grandison P . Identification of a new fibroblast growth factor receptor, FGFR5. Gene. 2001; 271(2):171-82. DOI: 10.1016/s0378-1119(01)00518-2. View

Duchesne L, Tissot B, Rudd T, Dell A, Fernig D . N-glycosylation of fibroblast growth factor receptor 1 regulates ligand and heparan sulfate co-receptor binding. J Biol Chem. 2006; 281(37):27178-89. DOI: 10.1074/jbc.M601248200. View

Hammerman P, Sos M, Ramos A, Xu C, Dutt A, Zhou W . Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2012; 1(1):78-89. PMC: 3274752. DOI: 10.1158/2159-8274.CD-11-0005. View

Kumar R, Knick V, Rudolph S, Johnson J, Crosby R, Crouthamel M . Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther. 2007; 6(7):2012-21. DOI: 10.1158/1535-7163.MCT-07-0193. View

Fischer H, Taylor N, Allerstorfer S, Grusch M, Sonvilla G, Holzmann K . Fibroblast growth factor receptor-mediated signals contribute to the malignant phenotype of non-small cell lung cancer cells: therapeutic implications and synergism with epidermal growth factor receptor inhibition. Mol Cancer Ther. 2008; 7(10):3408-19. PMC: 2879863. DOI: 10.1158/1535-7163.MCT-08-0444. View

Hanna N, Kaiser R, Sullivan R, Aren O, Ahn M, Tiangco B . Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): A randomized, double-blind, phase III trial. Lung Cancer. 2016; 102:65-73. DOI: 10.1016/j.lungcan.2016.10.011. View

Lemmon M, Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2010; 141(7):1117-34. PMC: 2914105. DOI: 10.1016/j.cell.2010.06.011. View

Travis W . Pathology of lung cancer. Clin Chest Med. 2011; 32(4):669-92. DOI: 10.1016/j.ccm.2011.08.005. View

10.

Schildhaus H, Heukamp L, Merkelbach-Bruse S, Riesner K, Schmitz K, Binot E . Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Mod Pathol. 2012; 25(11):1473-80. PMC: 4089812. DOI: 10.1038/modpathol.2012.102. View

11.

Lieu C, Heymach J, Overman M, Tran H, Kopetz S . Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res. 2011; 17(19):6130-9. PMC: 5562355. DOI: 10.1158/1078-0432.CCR-11-0659. View

12.

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M . Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2012; 381(9863):303-12. DOI: 10.1016/S0140-6736(12)61900-X. View

13.

Marchetti A, Martella C, Felicioni L, Barassi F, Salvatore S, Chella A . EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol. 2005; 23(4):857-65. DOI: 10.1200/JCO.2005.08.043. View

14.

Wang R, Wang L, Li Y, Hu H, Shen L, Shen X . FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer. Clin Cancer Res. 2014; 20(15):4107-14. DOI: 10.1158/1078-0432.CCR-14-0284. View

15.

Zhao G, Li W, Chen D, Henry J, Li H, Chen Z . A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models. Mol Cancer Ther. 2011; 10(11):2200-10. DOI: 10.1158/1535-7163.MCT-11-0306. View

16.

Reck M, Kaiser R, Mellemgaard A, Douillard J, Orlov S, Krzakowski M . Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014; 15(2):143-55. DOI: 10.1016/S1470-2045(13)70586-2. View

17.

Kuhn H, Kopff C, Konrad J, Riedel A, Gessner C, Wirtz H . Influence of basic fibroblast growth factor on the proliferation of non-small cell lung cancer cell lines. Lung Cancer. 2004; 44(2):167-74. DOI: 10.1016/j.lungcan.2003.11.005. View

18.

Jonker D, Rosen L, Sawyer M, de Braud F, Wilding G, Sweeney C . A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors. Ann Oncol. 2010; 22(6):1413-1419. PMC: 3139984. DOI: 10.1093/annonc/mdq599. View

19.

Burris 3rd H, Dowlati A, Moss R, Infante J, Jones S, Spigel D . Phase I study of pazopanib in combination with paclitaxel and carboplatin given every 21 days in patients with advanced solid tumors. Mol Cancer Ther. 2012; 11(8):1820-8. DOI: 10.1158/1535-7163.MCT-11-0997. View

20.

Schlumberger M, Tahara M, Wirth L, Robinson B, Brose M, Elisei R . Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015; 372(7):621-30. DOI: 10.1056/NEJMoa1406470. View