更新于：2024-11-01

IGF-1R x FAK1

更新于：2024-11-01

基本信息

关联

项与 IGF-1R x FAK1 相关的药物

INT-231

靶点

FAK1 x IGF-1R

作用机制

FAK1抑制剂 [+1]

在研机构-

原研机构

University of Florida

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 IGF-1R x FAK1 相关的临床结果

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100 项与 IGF-1R x FAK1 相关的转化医学

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0 项与 IGF-1R x FAK1 相关的专利（医药）

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项与 IGF-1R x FAK1 相关的文献（医药）

2022-12-01·BMC Cancer

PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis

Article

作者: Sohn, Eun Jung

AbstractBackgroundOvarian cancer is the most lethal gynecologic disease and is one of the most commonly diagnosed cancers among women worldwide. The phosphatidylinositol 3-kinase (PI3K) family plays an important regulatory role in various cancer signaling pathways, including those involved in ovarian cancer development; however, its exact function remains to be fully understood. We conducted this study to understand the role of P13K in the molecular mechanisms underlying ovarian cancer development.MethodsTo determine the differential gene expression of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, in normal, tumor, and metastatic ovary tissues, TNM plotter analysis was performed. The microarray dataset GSE53759 was downloaded from Gene Expression Omnibus. ROC plotter analysis was conducted to understand the potential of PIK3R3 as a predictive marker for effectiveness of therapy in ovarian cancer. muTarget was used to identify mutations that alter PIK3R3 expression in ovarian cancer. To determine the interacting partners for PIK3R3 in ovarian tissues, the interactome-atlas tool was used. The Kyoto encyclopedia of genes and genomes (KEGG) analysis was conducted to identify the pathways in which these interacting partners were primarily enriched.ResultsPIK3R3 was overexpressed in ovarian and metastatic tumors. Elevated PIK3R3 levels were observed in ovarian cancer stem cells, wherein inhibiting PIK3R3 expression significantly reduced the size of ovarian cancer spheroids. Treatment of ovarian cancer stem cells with PF-04691502 (10 μM), an inhibitor of both PI3K and mTOR kinases, also reduced the size of spheroids and the level of OCT4. PIK3R3 was highly expressed in ovarian cancer with several somatic mutations and was predicted better outcomes in patients undergoing Avastin® chemotherapy using bioinformatic tool. Protein interaction analysis showed that PIK3R3 interacts with 157 genes, including GRB2, EGFR, ERBB3, PTK2, HCK, IGF1R, YES1, and PIK3CA, in the ovary. KEGG enrichment analysis revealed that the interacting partners of PIK3R3 are involved in the ErbB signaling pathway, proteoglycans in cancer, FoxO, prolactin, chemokine, and insulin signaling pathways.ConclusionsPIK3R3 plays a pivotal role in ovarian cancer development and is therefore a potential candidate for developing novel therapeutic approaches.

2022-01-01·Theranostics1区 · 医学

Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2

1区 · 医学

ArticleOA

作者: Zhang, Bixiang ; Li, Dongxiao ; Tian, Dean ; Xia, Limin ; Xie, Meng ; Chen, Xiaoping ; Sun, Mengyu ; Zhang, Tongyue ; Ji, Xiaoyu ; Huang, Wenjie ; Wang, Yijun

Background: Accumulating studies manifest that BTB and CNC homology 1 (BACH1) facilitates multiple malignancies progression and metastasis, and targeting the BACH1 pathway enhances antitumor efficacy. Nevertheless, the exact mechanism of BACH1 promoting growth and metastasis and its therapeutic significance in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression of BACH1 in human HCC specimens and HCC cell lines was analyzed by quantitative RT-PCR (RT-qPCR), western blot, and immunohistochemistry (IHC). The invasiveness and metastasis of HCC cells in vitro and in vivo were evaluated using transwell assays and orthotopic xenograft models. The luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays were performed to explore the transcriptional regulation of insulin-like growth factor 1 receptor (IGF1R) and protein tyrosine kinase 2 (PTK2) by BACH1. Results: BACH1 was prominently upregulated in human HCC samples and elevated BACH1 expression was associated with poor overall survival (OS) and high recurrence rates of HCC patients. BACH1 facilitated growth and metastasis of HCC by upregulating cell motility-related genes IGF1R and PTK2. Notably, insulin-like growth factor 2 (IGF2), the ligand of IGF1R, in turn upregulated BACH1 expression through the IGF1R-ERK1/2-ETS1 cascades, thus forming a positive feedback loop to provoke HCC growth and metastasis. Moreover, combining IGF1R inhibitor linsitinib with PTK2 inhibitor defactinib prominently suppressed BACH1-mediated HCC growth and metastasis. Conclusions: These results demonstrated the tumorigenic and pro-metastatic role of BACH1 in HCC, which could be a promising biomarker for predicting poor prognosis and selecting patients who could benefit from combination therapy of IGF1R-targeted and PTK2-directed.

2021-11-17·Journal of Oncology4区 · 医学

Identification of an Immune-Related Biomarker Model Based on the CircRNA-Associated Regulatory Network for Esophageal Carcinoma

4区 · 医学

ArticleOA

作者: Tang, Jia ; Xie, Jun ; Zhou, Kaiguo ; Hu, Zhaonian ; Han, Song ; Chen, Xiaochun

Esophageal carcinoma (ESCA) is one of the most frequent types of malignant tumor that has a dismal prognosis. This research applied datasets aimed from the GEO and TCGA to create a prognostic signature for forecasting the clinical outcome of ESCA patients on the basis of a circRNA-associated regulatory network. Methods. A regulatory network associated with ESCA was established based on transcriptome data of circRNAs, miRNAs, and mRNAs. Functional annotations were implemented to further explore the mechanism of ESCA. Cox relative regression method was applied to create a risk signature. Besides, the immune microenvironment of the signature was investigated by utilizing the CIBERSORT algorithm. Results. Based on 27 DEcircRNAs, 65 DEmiRNAs, and 780 DEmRNAs, the circRNA-miRNA-mRNA network was finally set up. Functional enrichment unearthed that the regulatory network might participate in phosphorylation negative regulation, MAPK pathway, and PI3K/AKT pathway. This study established a risk scoring signature based on the seven immune-related genes (IRGs) (MARP14, RASGR1, PTK2, HMGB1, DKK1, RARB, and IGF1R), which was validated for its reliability. A stable and accurate nomogram combining immune-related risk scores with clinical features was constructed. Furthermore, we observed that the risk model was also related to the immunocyte infiltration. Conclusion. Our study successfully created a circRNA-associated regulatory network and further developed an immune-related model to forecast the clinical outcome of ESCA patients as well as to assess their immune status.