Fibroblast Growth Factor Receptor 1 Gene Amplification Is Associated With Poor Survival and Cigarette Smoking Dosage in Patients With Resected Squamous Cell Lung Cancer

Kim, Hye Ryun; Kim, Dae Joon; Kang, Dae Ryong; Lee, Jin Gu; Lim, Sun Min; Lee, Chang Young; Rha, Sun Young; Bae, Min Sun; Lee, Young Joo; Kim, Se Hoon; Ha, Sang Jun; Soo, Ross A.; Chung, Kwansoo; Kim, Joo Hang; Lee, Ji Hyun; Shim, Hyo Sup; Cho, Byoung Chul

doi:10.1200/jco.2012.43.8622

Cited by 139 publications

(136 citation statements)

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“…Recently a meta-analysis showed that patients with FGFR gene amplification have a worse prognosis than FGFR wild-type patients. This gene alteration is also observed in other tumors like breast cancer (14%), urothelial cancer (7%) and ovarian cancer (5%) and squamous cell lung cancer (SCCL) (18.2%) Craddock et al, 2013;Heist et al, 2012;Kim et al, 2016a;Kim et al, 2016b;Monaco et al, 2016). In lung squamous cell carcinoma the presence of FGFR1 amplification doesn't change the patients' prognosis (Craddock et al, 2013).…”

Section: Fgfr In Cancermentioning

confidence: 82%

“…Sinapsine, an alkaloid derived from cruciferous' seeds, downregulates FGFR4 (Guo et al, 2016). FGFR resistance to AZD3437 has been found in lung cancer cell lines (H1581AR) due to MET amplification by activating ErbB3, in the same experiment, Kim et al found that a combination of a FGFR inhibitor and a Met inhibitor synergistically inhibited cell proliferation (Kim et al, 2016a;Kim et al, 2016b). In a small cell lung cancer group of patients with FGFR1 amplification treated with Nintedanib might occur a resistance.…”

Section: Resistance To Therapiesmentioning

confidence: 96%

“…In lung squamous cell carcinoma the presence of FGFR1 amplification doesn't change the patients' prognosis (Craddock et al, 2013). In another study it as been reported that FGFR1 is an independent negative prognostic factor in surgically resected SCCL and is associated with cigarette smoking (Kim et al, 2016a;Kim et al, 2016b). In gastric cancer, FGFR2 amplification was detected in 4.2-7.4% of cases and has been correlated with poor prognosis and lymphatic invasion (Su et al, 2014).…”

Section: Fgfr In Cancermentioning

confidence: 99%

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FGFR a promising druggable target in cancer: Molecular biology and new drugs

Porta

Borea²,

Coelho³

et al. 2017

Critical Reviews in Oncology/Hematology

179

162

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Introduction The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion Most of the TKR share intracellular signaling pathways; therefore, cancer cells tend to overcome the inhibition of one tyrosine kinase receptor by activating another. The future of TKI (Tyrosine Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that target different TKR simultaneously. It is crucial to understand the interaction of the FGF-FGFR axis with other known driver TKRs. Based on this, it is possible to develop therapeutic strategies targeting multiple connected TKRs at once. One correct step in this direction is the reassessment of multi target inhibitors considering the FGFR status of the tumor. Another opportunity arises from assessing the use of FGFR TKI on patients harboring FGFR alterations

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Section: Fgfr In Cancermentioning

confidence: 82%

Section: Resistance To Therapiesmentioning

confidence: 96%

Section: Fgfr In Cancermentioning

confidence: 99%

See 1 more Smart Citation

FGFR a promising druggable target in cancer: Molecular biology and new drugs

Porta

Borea²,

Coelho³

et al. 2017

Critical Reviews in Oncology/Hematology

179

162

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“…FISH has been the most frequently used method to detect FGFR1 amplification status, 9,10,21,22,[25][26][27] although alternative methods such as real-time polymerase chain reaction 24 and SISH 23 have also been used. SISH has several advantages over FISH including automation, use of bright-field microscopes in contrast to expensive FISH microscopes, signal permanence, and easier histologic comparison.…”

Section: Discussionmentioning

confidence: 99%

“…13,14 FGFR1 amplification has recently been reported by members of our group in oral squamous cell carcinoma, 15 but it has also been described in esophageal squamous cell carcinoma, ovarian cancer, bladder cancer, prostate cancer, and rhabdomyosarcoma. [16][17][18][19][20] Subsequent to the landmark initial studies, 9,10 other groups [21][22][23][24][25][26][27] have investigated FGFR1 amplification in non-small cell lung carcinoma, using different definitions of FGFR1 amplification generally utilizing FISH, but there have been reports utilizing silver in situ hybridization (SISH) 23 and real-time polymerase chain reaction. 24 The frequency of FGFR1 amplification in squamous cell carcinoma and its potential as an actionable molecular target highlight the importance of not only defining amplification but also determining the most reliable and reproducible method to detect its presence, as well as assessing which tumor subtypes to test.…”

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confidence: 99%

Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH

Russell

Young

et al. 2014

Modern Pathology

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The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 Z2, or tumor cell percentage with Z15 signals Z10%, or average number of signals/tumor cell nucleus Z6. Low-level amplification was defined as tumor cell percentage with Z5 signals Z50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; Po0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P ¼ 0.88, HR ¼ 1.04, 95% confidence interval (CI) ¼ 0.67-1.60) or overall survival (P ¼ 0.97, HR ¼ 1.01, 95% CI ¼ 0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method to detect FGFR1 amplification. No relationship was detected between patient outcome and FGFR1 amplification. Keywords: amplification; fibroblast growth factor receptor 1; squamous cell lung carcinomaIn Australia in 2009, lung cancer was the fifth most commonly diagnosed cancer, but it was the most common cause of cancer deaths for both men and women. 1 Approximately 85% of lung cancers are of non-small-cell carcinoma type, the subtypes of which are in reducing order of frequency: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, the latter being a morphologic diagnosis

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Fibroblast growth factor signaling and inhibition in non‐small cell lung cancer and their role in squamous cell tumors

Salgia

2014

Cancer Medicine

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With the introduction of targeted agents primarily applicable to non-small cell lung cancer (NSCLC) of adenocarcinoma histology, there is a heightened unmet need in the squamous cell carcinoma population. Targeting the angiogenic fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway is among the strategies being explored in squamous NSCLC; these efforts are supported by growth-promoting effects of FGF signaling in preclinical studies (including interactions with other pathways) and observations suggesting that FGF/FGFR-related aberrations may be more common in squamous versus adenocarcinoma and other histologies. A number of different anti-FGF/FGFR approaches have shown promise in preclinical studies. Clinical trials of two multitargeted tyrosine kinase inhibitors are restricting enrollment to patients with squamous NSCLC: a phase I/II trial of nintedanib added to first-line gemcitabine/cisplatin and a phase II trial of ponatinib for previously treated advanced disease, with the latter requiring not only squamous disease but also a confirmed FGFR kinase amplification or mutation. There are several ongoing clinical trials of multitargeted agents in general NSCLC populations, including but not limited to patients with squamous disease. Other FGF/FGFR-targeted agents are in earlier clinical development. While results are awaited from these clinical investigations in squamous NSCLC and other disease settings, additional research is needed to elucidate the role of FGF/FGFR signaling in the biology of NSCLC of different histologies.

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Fibroblast Growth Factor Receptor 1 Gene Amplification Is Associated With Poor Survival and Cigarette Smoking Dosage in Patients With Resected Squamous Cell Lung Cancer

Abstract: FGFR1 amplification is an independent negative prognostic factor in surgically resected SCCL and is associated with cigarette smoking in a dose-dependent manner. FGFR1 amplification is a relevant therapeutic target in Asian patients with SCCL.

Cited by 139 publications

References 28 publications

FGFR a promising druggable target in cancer: Molecular biology and new drugs

FGFR a promising druggable target in cancer: Molecular biology and new drugs

Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH

Fibroblast growth factor signaling and inhibition in non‐small cell lung cancer and their role in squamous cell tumors

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