FGFR2 gene amplification, and resulting FGFR2 protein overexpression, is rare in gastric cancer patients, and development of an accurate and widely available method for mass screening to identify patients who may respond to treatment with fibroblast growth factor receptor (FGFR) inhibitors is important The fibroblast growth factor receptor (FGFR) pathway plays a key role in gastric cancer pathogenesis, with 1.2%-9% of gastric cancer patients harbouring FGFR2 amplifications. Several selective FGFR inhibitors have been developed in the last years, with promising efficacy signals Purpose: FGFRgene aberrations are associated with tumor growth and survival. We explored the role ofFGFR2ampliﬁcation in gastric cancer and the therapeutic potential of AZD4547, a potent and selective ATP-competitive receptor tyrosine kinase inhibitor of ﬁbroblast growth factor receptor (FGFR)1-3, in patientswithFGFR2-ampliﬁed gastric cancer FGFR2 gene amplification, and resulting FGFR2 protein overexpression, is rare in gastric cancer patients, and development of an accurate and widely available method for mass screening to identify..
PURPOSE: The aim of this study was to use immunohistochemistry (IHC) to determine the effect of FGFR2 and VEGFR2 expression on treatment outcomes for patients with metastatic or recurrent advanced gastric cancer (AGC) receiving a combination of pazopanib with CapeOx (capecitabine and oxaliplatin) FGFR2-Amplified Gastric Cancer Cell Lines Require FGFR2 and Erbb3 Signaling for Growth and Survival Kaiko Kunii,1 Lenora Davis,2 Julie Gorenstein,3 Harold Hatch,2 Masakazu Yashiro,4 Alessandra Di Bacco,1 Cem Elbi,3 and Bart Lutterbach2 1Pharmacology, 2Cancer Biology and Therapeutics, and 3Cancer Pathways, Merck Research Laboratories, Boston, Massachusetts; an Fibroblast growth factor receptor 2 (FGFR2) amplification has been reported to be a target for treatment in gastric cancer. However, an optimal tissue source and method for evaluating FGFR2 have yet to be established Fibroblast growth factor receptor type 2 (FGFR2) has emerged as a key oncogenic factor that regulates gastric cancer (GC) progression, but the underlying mechanism of FGF-FGFR2 signaling pathway remains largely unknown
TPS4135 Background: FGFR2b overexpression and FGFR2 gene amplification occurs in approximately 10% of patients with gastric cancer (GC) and is associated with a poor prognosis and the presence of metastases FGFR2b is a splice isoform of FGFR2 found to be overexpressed in up to 60% of gastric cancer cases depending on the assay used and the stage of disease. Overexpression of the receptor promotes aberrant signaling through the RAS/MAPK and PI3K/AKT/mTOR pathways, ultimately resulting in tumor cell proliferation FGFR2 was originally identified as an amplified DNA sequence from the gastric cancer cell line KatoIII (18, 20), and subsequent efforts identified FGFR2 amplification in 3% to 10% of primary gastric cancers (12, 16, 21) FGFR2 (fibroblast growth factor receptor 2 gene) encodes the fibroblast growth factor receptor 2 protein, a receptor tyrosine kinase.FGFR2 and other FGFR TKs play crucial roles in development and have been shown in cancers to be deregulated by amplification, point mutation, or translocation (PMID: 20094046).). Amplification or activation of FGFR2 has been reported in breast cancer and gastric.
Introduction. Gastric cancer (GC) is the fifth most prevalent cancer and the third leading cause of cancer-related death worldwide ().Although surgery is the treatment of choice for GC, prognosis with advanced GC is still poor ().It has been reported that 22-51% of GC patients who received radical surgery with curative intent develop recurrent disease (3, 4) Expression of FGFR2 (BEK, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers
FGFR2 amplification has been found in diffuse-type gastric cancer-derived cell lines and the amplification was preferentially detected in diffuse-type gastric cancer. FGFR2 protein overexpression. FGFR2 Fusion is an inclusion criterion in 4 clinical trials for gastric carcinoma, of which 4 are open and 0 are closed. Of the trials that contain FGFR2 Fusion and gastric carcinoma as inclusion criteria, 1 is phase 1 (1 open), 1 is phase 1/phase 2 (1 open), and 2 are phase 2 (2 open) [ 5 ]. Cancer + FGFR2 amplification has been found in diffuse-type gastric cancer-derived cell lines and the amplification was preferentially detected in diffuse-type gastric cancer. FGFR2 protein overexpression was detected using immunohistochemical staining in 20 of 38 advanced cases of diffuse-type gastric cancer (Hattori et al, 1996). FGFR2 The FGFR2 inhibitors AZD4547 and BGJ398 significantly decreased the growth of OCUM-14 cells, while paclitaxel and 5-fluorouracil significantly decreased the proliferation of OCUM-14 cells, but cisplatin did not. CONCLUSION: A new gastric cancer cell line, OCUM-14, was established from SGC and showed FGFR2 overexpression
Genetic mutations and amplifications of receptor tyrosine kinase fibroblast growth factor 2 (FGFR2) are associated with tumorigenesis, 1-3 and inhibitors targeting FGFR2 are being developed. 4-6 FGFR2 genetic variations and alterations have also been reported in gastric cancer.Mutations in FGFR2 have been reported, 7 but these were anecdotal findings, and most of the larger scale studies. Dovitinib for Gastric Cancer With FGFR2 Amplification: GASDOVI-1 The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials FGFR2 gene amplification was initially found in a gastric cancer cell line originating from diffuse type gastric cancer . FGFR2 has been demonstrated to be a poor prognostic biomarker (10,11) and antibodies (12-14) or small molecule inhibitors (15-18) targeting FGFR2 can suppress gastric cancer progression in vivo and in vitro e15074. Background: Amplification of the Fibroblast Growth Factor Receptor 2 (FGFR2) gene is reported in ~5% of gastric cancer patients and leads to the specific overexpression of the FGFR2b isoform of the receptor.Five Prime Therapeutics has developed an FGFR2b-specific antibody, FPA144, for treating gastric cancer patients with FGFR2 amplification. . We are also investigating the utility of.
We have identified a critical role for amplified FGFR2 in gastric cancer cell proliferation and survival. In a panel of gastric cancer cell lines, fibroblast growth factor receptor 2 (FGFR2) was overexpressed and tyrosine phosphorylated selectively in FGFR2-amplified cell lines KatoIII, Snu16, and OCUM-2M. FGFR2 kinase inhibition by a specific small-molecule inhibitor resulted in selective and. vehicle. Regorafenib effectively abrogates activated FGFR2 signaling in FGFR2-ampliﬁed gastric and colorectal cancer and, therefore, might be considered for integration into treatment in patients with FGFR2-ampliﬁed gastric and colorectal cancers. 1. Introduction Regorafenib (BAY 73-4306) is an orally bioavailable
C, Detection of FGFR2 + gastric cancer cells in the peripheral blood of a healthy volunteer by flowcytometry. FGFR2 + cells of OCUM-2MD3, KATO-III, MKN45, and NUGC3 were detected (101 cells, 177 cells, 4 cells, and 9 cells of a total of 250 cells, respectively) . Gastric cancer is the second leading cause of death from cancer worldwide. Amplification of the FGFR2 gene has been reported in ∼ 5 to 7% of gastric cancers, and several studies have also reported overexpression of the FGFR2 protein using immunohistochemistry (IHC)
As with other uncommon molecular subsets, the relatively low incidence of FGFR2 amplification in gastric cancer specimens may present a hurdle in developing FGFR2-targeted therapies in gastroesophageal cancer . We do note that the 5% frequency is similar to ALK-rearranged, and greater than ROS1-rearranged lung cancers, subtypes for which. A study that was presented during the [2021 Gastrointestinal Cancers Symposium evaluated] FGFR2-altered gastric cancer. [The data showed that] the addition of an FGFR inhibitor to FOLFOX.
FGFR2 signals reported to be required for the proliferation of SGC cells. 14-16 S1, a 5-FU analog, has recently become first-line chemotherapy for gastric cancer patients at advanced stage. 9 In this study, the combined administration of Ki23057 and S1 decreased orthotopic tumor growth as well as LN metastasis more effectively than either. Since patients with FGFR2-positive gastric cancer show poor prognosis,7, 15, 16 FGFR2 is considered to be one of the molecular targets for gastric cancer, especially for SGC; however, only three existing SGC cell lines have been reported to overexpress FGFR2.16,17, - 18 Establishment of a new SGC cell line with FGFR2 overexpression will be. . The aim of the present study was to explore the effects of miR‑494 and FGFR2 in regulation of cancer‑initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2‑positive gastric cancer B, Determination of FGFR2+ cells in peripheral blood of a healthy volunteer by flowcytometry. No FGFR2+ cell was detected when the cutoff value of FGFR2+ fluorescence was 1000. C, Detection of FGFR2+ gastric cancer cells in the peripheral blood of a healthy volunteer by flowcytometry. FGFR2+ cells of OCUM-2MD3, KATO-III, MKN45, and NUGC
Frontline Bemarituzumab Doublet Prolongs Survival in Advanced FGFR2b+ Gastric/GEJ Cancer. In the frontline setting of FGFR2b-positive advanced gastric or gastroesophageal junction adenocarcinoma, the combination of bemarituzumab combined with mFOLFOX6 achieved a 56% reduction in the risk of disease progression or death compared with placebo. In. metastatic gastric cancer is only 10 months . Given this, there is an urgent need to improve gastric cancer therapy. FGFR2 ampliﬁcation occurs in 3-10 % of primary gastric cancers, and has been reported to be more frequent in the undifferentiated diffuse subtype . The effective-ness of FGFR inhibitors against gastric cancer in vitro an Gastric 25, rectal 26 and breast cancer 20 cell lines with high levels of amplification of FGFR2 are highly sensitive to selective FGFR inhibitors in vitro and in vivo, which suggests that FGFR2. FGFR2 is frequently amplified in gastric cancer cell lines, especially in poorly differentiated type cells and amplification confers hypersensitivity to FGFR inhibitors (16,22). Regarding the mutation of FGFR2 , somatic mutations of FGFR2 have been found in 12% (15/122) of endometrial carcinomas and these FGFR2 mutations have an oncogenic. Amplification of fibroblast growth factor receptor2 (FGFR2) has been regarded as a druggable target in gastric cancer (GC). Despite known potential of AZD4547, a selective inhibitor of FGFR 1-3, to suppress tumorigenic effects of activated FGFR2, resistance to the targeted agent has been an unresolved issue
In conclusion, CD44 and FGFR2 maintain stemness in gastric cancer by differentially regulating c-Myc transcription. AB - Despite their suggested importance, the mechanistic roles of FGFR2 and gastric cancer stem cell (GCSC) marker CD44 remain unclear. We investigated cross talk between CD44 and FGFR2 Fibroblast growth factor 7 (FGF7) is a mesenchyme-specific heparin-binding growth factor that binds FGF receptor 2 (FGFR2) to regulate numerous cellular and physiological processes. FGF7/FGFR2 signal is associated with gastric cancer progression. In the present study, we investigated the molecular mechanism by which FGF7/FGFR2 promotes invasion and migration in human gastric cancer
Patients and Methods: FGFR2 amplification was tested by qPCR using TaqMan probe and dual-color FISH in a panel of 37 gastric cancer cell lines and tumor specimens from 482 gastric cancer patients. Results: Of the 482 patients, 119 (24.8%) of the patients had FGFR2 copy number greater than 3.0 copies . FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond A total of 1-9 biopsies were obtained from each of 166 patients with gastric tumors over an 8 year period. A threshold of >50 tumor cells was used for inclusion. MET positivity by IHC was defined as a score of 3+ and positivity by FISH was an average copy number ≥5. FGFR2 positivity was defined as ≥6 copies
FGFR amplification has been reported in various cancers, including FGFR1 amplification in estrogen receptor-positive breast cancer and squamous cell lung cancer, and FGFR2 amplification in triple negative breast cancer and gastric cancer (Wang et al., 2014) EGFR-targeted Therapy for Gastric Cancer. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government The addition of bemarituzumab to modified FOLFOX6 benefited patients with advanced gastric and gastroesophageal junction cancer with FGFR2b overexpression. The study was originally launched as a.
The Swiss company will assess the agent both alone and combined with Tecentriq as a treatment for FGFR-positive gastric cancer. FGFR2, and FGFR3, both as a monotherapy and in combination with the PD-L1 inhibitor atezolizumab (Roche's Tecentriq). Basilea will sponsor the study, while Roche will supply atezolizumab Preclinical models of diffuse-type gastric cancer (DGC) that reliably predict clinical activity of novel compounds are lacking. To overcome the problem of poor tumor cellularity in DGC, we used cells from malignant ascites to establish DGC patient-derived xenograft (PDX) models that recapitulate the primary cancer. Cells in PDX model GAGA6 with FGFR2 amplification were sensitive to AZD4547, a. Results: FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. The copy number assay revealed that 4.1% (11 out of 267) of the gastric cancers harboured FGFR2 amplification. No amplification of the three other family members (FGFR1, 3 and 4) was detected.A FISH analysis was performed on 7 cases among 11 FGFR2-amplified cases and showed that 6 of these 7. 65. Background: The aim of this study was to use immunohistochemistry (IHC) to determine the effect of FGFR2 and VEGFR2 expression on treatment outcomes for patients with metastatic or recurrent advanced gastric cancer (AGC) receiving a combination of pazopanib with CapeOx (capecitabine and oxaliplatin).Methods: We conducted a single-arm, open-label phase II study to determine the efficacy and.
Patients were divided based on level of expression into one of the two groups low (under cut off) or high (over cut off). X-axis shows time for survival (years) and y-axis shows the probability of survival, where 1.0 corresponds to 100 percent. Read more. FGFR2 is not prognostic in stomach cancer. Alive (n=208 The aim of this study was to use immunohistochemistry (IHC) to determine the effect of FGFR2 and VEGFR2 expression on treatment outcomes for patients with metastatic or recurrent advanced gastric cancer (AGC) receiving a combination of pazopanib with CapeOx (capecitabine and oxaliplatin). We conducted a single-arm, open-label phase II study to determine the efficacy and toxicity of the. Proto-oncogene activation can occur by amplification of a large tract of DNA: the purpose of this study was to determine the structure of the FGFR2 amplicon in the gastric cancer cell line SNU-16. Methods. FGFR2 amplification was confirmed by Southern blotting. Fluorescence in situ hybridization was used to visualize the locations of the SNU-16. In this study, expression status of FGFR2 and HER2 in advanced/metastatic gastric cancer (GC) and colorectal cancer (CRC) were prospectively analyzed in clinical setting. Moreover, eligible patients for the clinical trials of DS-1123 or DS-8201, which are FGFR2- or HER2-targeting anti-cancer agent respectively, were screened in stage/IIIII gastric cancer. Patients with FGFR2 3+ in stage II/III gastric cancer should carefully be followed‑up for >5 years after surgery. Introduction Gastric cancer is one of the leading causes of cancer related death worldwide (1). Advanced gastric cancer exhibits poor prognosis, and even optimal combination modalities o
Interestingly, there was no evidence of FGFR2 mutations in 38 gastric cancer cell lines, which argues in favor of amplification rather than mutation as the preferred mechanism of FGFR2 activation in a subset of gastric cancer. In contrast, FGFR2 activation is mainly associated with oncogenic mutations in endometrial and breast cancers FGFR2 Mutation. Fibroblast growth factor receptor 2 (FGFR2) mutations occur in several cancer types that cause the FGFR2 protein to be more active, leading to cancerous cells that grow and divide quickly. In normal cells, the FGFR2 proteins facilitate cell growth, division, maturation, and the development of bones and blood vessels
P79. FGFR2 Amplification in Gastric Cancer. P.S. Dahlberg, MD, PhD, L.J. Ferrin, MD, PhD, G. Dahal, PhD. University of Minnesota. Introduction. Proto-oncogene activation can occur by amplification of a large tract of DNA: the purpose of this study was to determine the structure of the FGFR2 amplicon in the gastric cancer cell line SNU-16 The FGFR2 inhibitor Ki23057 might be therapeutically promising for treating drug-resistant gastric cancer cells, especially when used in combination with SN38, PTX, or VP16. The apoptosis process might be the main mechanism underlying the synergistic effect of these combinations FGFR2 is a transmembrane RTK, and overexpression has been associated with a poor prognosis in gastric cancer 9, 13. Substantial preclinical work has suggested higher-level clonal FGFR2 amplification predicts response to FGFR2 inhibitors across several tumor types, including GEA 14 - 16 Therapeutic Targeting of Fibroblast Growth Factor Receptors in Gastric Cancer. Mikito Inokuchi,1 Yoshitaka Fujimori,1 Sho Otsuki,1 Yuya Sato,1 Masatoshi Nakagawa,1 and Kazuyuki Kojima2. 1Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Missense mutations of FGFR2 have been found in endometrial cancer and melanoma. As a drug target. AZD4547 is a tyrosine kinase inhibitor which targets FGFR1-3. It has demonstrated early evidence of efficacy in gastric cancer patients with high level FGFR2 amplification (Cancer Discovery 2016) The amplifications of genes encoding RTKs, such as EGFR, ERBB2, FGFR2 and MET, occur in gastric cancer (47,48). Gastric cancer with FGFR2 amplification is significantly associated with lymphatic invasion and a poor prognosis (49,50); however, the molecular mechanisms through which FGFR2 amplification promotes lymph node metastasis remain unclear FGFR2 in gastric cancer: Protein overexpression predicts gene amplification and high H-index predicts poor survival. Soomin Ahn, Jeeyun Lee, Mineui Hong, Seung Tae Kim, Se Hoon Park, Min Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Sin Ho Jung, Won Ki Kang, Kyoung Mee Kim The FGFR2 gene is abnormally active (overexpressed) in certain types of stomach (gastric) cancers, and this amplification is associated with a poor disease outcome. Abnormal expression of the FGFR2 gene is also found in patients with prostate cancer. A shift in the expression of two specific FGFR2 isoforms, IIIb and IIIc, appears to correlate.