IGF1R overexpression

Circ_0005615 downregulation blocked MM development by targeting miR-331-3p/IGF1R axis.

This strategy optimizes cancer cell-specific delivery to block proliferation and immune checkpoints. The results support further preclinical proof-of-concept studies to enable an eIND submission for the anti-miR-21 RNA-peptide analog.

This review will detail experience using the alpha emitter radium-223 (Ra, tradename Xofigo), that targets bone formation, in osteosarcoma, specifically related to patient selection, use of gemcitabine for radio-sensitization, and using denosumab to increasing the osteoblastic phenotype of these cancers. A case of an inoperable left upper lobe vertebral-paraspinal-mediastinal osteoblastic lesion treated successfully with Ra combined with gemcitabine is described. Because not all areas of osteosarcoma lesions are osteoblastic, but nearly all osteosarcoma cells overexpress IGF1R, and some subsets expressing Her-2, the anti-IGF1R antibody FPI-1434 linked to actinium-225 (Ac) or the Her-2 antibody linked to thorium-227 (Th) may become other means to provide targeted alpha particle therapy against osteosarcoma (NCT03746431 and NCT04147819).

We demonstrate that combined trametinib and ganitumab is effective in a genomically diverse panel of RAS-mutated FN RMS preclinical models.

On the other hand, MEK (mitogen-activated protein kinase kinase)1/2 inhibitors, including PD0325901, selumetinib, trametinib and TAK-733, selectively antagonized IGF1R signaling-mediated antiestrogen resistance but did not affect cell proliferation under normal growth conditions. In a group of 219 patients with metastasized ER+ breast cancer, strong pMEK staining showed a significant correlation with no clinical benefit of first-line tamoxifen treatment. We propose a critical role for MEK activation in IGF1R signaling-mediated antiestrogen resistance and anticipate that dual-targeted therapy with a MEK inhibitor and antiestrogen could improve treatment outcome.

In this review, we summarize the biological roles of the IGF axis in NSCLC, including the expression and prognostic significance of the related components, noncoding RNA regulation, involvement in drug resistance, and therapeutic application. This review offers a comprehensive understanding of NSCLC and provides insightful ideas for future research.

IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.

We emphasized the oncogenic role of IGF2BP2 in gastric carcinogenesis and confirmed its activation is partly due to the activation of IGF1R-RhoA-ROCK signaling pathway. Our findings identified that IGF2BP2 might be a promising prognostic biomarker and provided clinical translational potential.

In conclusion, the promoting effects of IGF1R on OS are targeted by miR-6838-5p. CircRASSF2 restored the expression of IGF1R by sponging miR-6838-5p, thereby promoting the progression of OS.

The downstream effector, phospho-MAPK44/42 was also increased in uteri of treated rats. Our findings show RTKs are dysregulated following early life TBBPA exposures and their sustained activation may contribute to TBBPA-induced uterine tumors observed in rats later in life.

Picropodophyllin, a specific inhibitor of IGF1R, increased the expression of p-ERK protein, and decreased the transcription level of interleukin-6...The high expression of IGF1R in tumor cell stem-like cells might inhibit the expression of p-ERK and promote the generation of inflammatory factors. Insulin-like growth factor type 1 receptor plays a stemness maintenance role in ACP and regulates the production of inflammatory factors through a p-ERK pathway, which suggests that targeting IGF1R and p-ERK might provide a new direction for alleviating tumor inflammation.

miR-99a can specifically inhibit IGF1R expression and thus inhibit the proliferation and migration of CCCs.

Our studies suggest that miR-769-5p/miR-769-3p acts as a tumor suppressor by the STAT3-IGF1R-HDAC3 complex. Moreover, SAHA triggers miR-769-5p/miR-769-3p-mediated inhibition of proliferation and induces apoptosis in GC cells.

The results of rescue experiments demonstrated that IGF‑1R overexpression reversed the suppressive effects of SNHG11 knockdown on the proliferation, migration and invasion of PCa cells. On the whole, the findings of the present study suggest that SNHG11 expression is upregulated in PCa and that it facilitates PCa progression, at least in part, via the modulation of the miR‑184/IGF‑1R signaling axis.

Bright‑field PLA analysis on a paraffin‑embedded tissue microarray from patients with colorectal cancer revealed a significant association between increased nuclear colocalizing signals of NuMA‑53BP1 and a shorter overall survival. These results indicate that nIGF1R plays a role in facilitating 53BP1‑dependent DDR by regulating the NuMA‑53BP1 interaction, which in turn might affect the clinical outcome of patients with colorectal cancer.

Moreover, miR-9-3p as the target of DUXAP8 and IGF1R as the target of miR-9-3p were verified in HCC cells. lncRNA DUXAP8 contributed to HCC tumorigenesis via the miR-9-3p/IGF1R axis, providing a novel therapeutic approach for HCC diagnosis and treatment.

In summary, we found that CASC11 is upregulated in PCa cells and clinical tumor samples in comparison to corresponding controls and revealed that ectopic CASC11 overexpression promotes cellular phenotypes associated with PCa progression through CASC11/miR-145/IGF1R axis.

In addition, loss of LINC01291 decreased the chemoresistance of melanoma cells to cisplatin...Rescue experiments revealed that the roles induced by LINC01291 depletion in melanoma cells could be reversed by suppressing miR-625-5p or overexpressing IGF-1R. Our study identified the LINC01291/miR-625-5p/IGF-1R competing endogenous RNA pathway in melanoma cells, which may represent a novel diagnostic biomarker and an effective therapeutic target for melanoma.

Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis.

Furthermore, our results provide a roadmap for immunotherapy of MM by unbiasedly comparing the expression of top MM cell surface targets in patient data and normal cells and suggest that the genetic landscape of MM may predict the expression of specific targets for precision immunotherapy. The quest for novel MM targets for immunotherapies remains open, and CAR target discovery driven by specific genetic events remains an active area of investigation.

On the contrary, miR-520b can downregulate the expression of IGF-1R. miR-520b increases DOX sensitivity and promotes cell apoptosis in breast cancer by inhibiting IGF-1R expression by the PI3K/AKT signaling pathway.

The present study confirmed that the "MIAT/miR-488-3p/IGF1R" pathway was involved in the development of CRC, which may be the target for developing therapeutic approaches for CRC.

Bufothionine promoted GC cell death by triggering miR-133a-3p/IGF1R/PI3K/Akt axis mediated ER stress and ROS production.

The study validates that miR-139-5p could suppress malignant melanoma progression through the repression of the PI3K/AKT signaling pathway by down-regulating IGF1R. Therefore, miR-139-5p could pave a new way for the treatment of malignant melanoma.

In conclusion, IGF-MTX at 0.20 μM equivalents per kg was well tolerated, caused no cytopenia, and produced stable disease and extension of life.

Our finding suggested decreased expression of XPO5 prevents maturation of miR-378a-3p, which leaded to the overexpression of IGF-1R and counteracted the effects of sorafenib-induced apoptosis. LXRα was able to activate miRNA-378a-3p transcription in HCC cells and could be a potential combinable treatment strategy with sorafenib to suppress HCC progression.

Additionally, low specific activity radioimmunoconjugate led to complete tumor remission in 2/6 mice. The data suggest that efficacy of cixutumumab can be enhanced by radiolabeling with 225Ac at a low specific activity.

In conclusion, we present a plausible mechanism for the interplay between TF and IGF-1R involving FVIIa, β1-integrins, Src family proteins, and caveolin-1. Our results increase the knowledge of diseases associated with TF and IGF-1R overexpression in general but specifically of TF-mediated signaling with focus on cell survival.