Application of FGFR2 inhibitors for cancer treatment in patients with FGFR2 mutation or gene amplification is beneficial; however, that for cancer prevention in people with FGFR2 risk allele might be disadvantageous due to the impediment of a cytoprotective mechanism against oxidative stress.
In vitro mechanistic assays demonstrated upregulation of γH2A.X and induction of cell cycle arrest in several FGFR2-expressing cancer cell lines after treatment with FGFR2-TTC.
More sophisticated patient selection strategies would help improve FGFR2-targeted therapies and combination therapy is considered the most promising approach for cancer patients with FGFR2 alterations.
This further suggests that epithelial cell resident, homeostasis-promoting FGFR2 may be involved in suppression of malignancy and that restoration may be a candidate for gene therapy of hormone-refractory prostate cancer.
High-level amplification of FGFR2 is relatively rare in gastric and breast cancers, and we show that screening for amplification in circulating tumor DNA may present a viable strategy to screen patients.Cancer Discov; 6(8); 838-51.
FGFR-2 IIIc was abundant in the cancer cells from 83 of 117 PDAC cases, which correlated with decreased duration to development of liver metastasis after surgery.
In 18 evaluable patients with FGFR genetic alterations, 3 confirmed partial responses (two intrahepatic cholangiocarcinomas (iCCA) with FGFR2 fusions and one urothelial cancer with FGFR2 and FGF19 amplification) and two durable stable disease at ⩾16 weeks with tumour reduction (FGFR2 fusion-positive iCCA and adrenocortical carcinoma with FGFR1 amplification) were observed.
The logistic regression confirmed that rs2981582FGFR2 polymorphism (OR = 2.09; 95 % CI 1.35, 3.20) and the interaction between rs1056663 and rs2708861 HUS1 polymorphisms increased the risk of cancer (OR = 1.87; 95 % CI 1.19, 2.92).
We found that FGF1-induced FGFR2 phosphorylation in either line resulted in significant activation of MMP7 and MMP26 and consequently an increase in cancer invasiveness.
Genetic alterations restricted to the brain metastases included mutations in cancer genes <i>FGFR2, PIK3CA</i> and <i>ATR</i>, homozygous deletion in <i>CDKN2A</i> and amplification in <i>KRAS</i>.
A growth inhibitory assay showed that only one FGF3/FGF4-amplified and three FGFR2-amplified cancer cell lines exhibited hypersensitivity to sorafenib in vitro.
Taken into account with our recent discovery of activating FGFR2 mutations in endometrial cancer, we suggest that FGFR2 may join the list of genes that play context-dependent opposing roles in cancer.
In the present article, we introduce our data on mutant epidermal growth factor receptor (EGFR) signaling and amplification of fibroblast growth factor receptor 2 (FGFR2) using microarray analysis, and treatment stratification and clinical applications using gene expression profiles for cancer treatments are discussed.
The FGFR2 IIIc protein was detected in all invasive cervical cancer patients (29 cases) and its mRNA was found to be strongly expressed in the invasive front of cancer cell nests.
The overexpression of FGFR2 promoted the generation of cancer‑initiating cells (CICs) and resistance to lapatinib in HER2‑positive gastric cancer YCC1 cells.