IGF1R expression

Consistently, nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner. Overall, our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

Our findings suggest that miR-221, miR-320a, miR-133a, miR-133b and their targets P27kip1, TGFBR1, and IGF1R might play a critical role in the development and progression of leiomyosarcoma. It provides a plausible basis for the use of the miRNAs investigated as biomarkers in leiomyosarcoma diagnostics.

Additionally, elevated IGF1R expression promotes NK cell expansion and enhances its functional activation, thereby inhibiting AML cell proliferation. Collectively, these findings highlight the clinical potential of IGF1R in the effective treatment of AML through the activation of NK cell proliferation and function and suggest that it may represent a potential predictive marker of AML prognosis.

The detection of THRIL in serum is useful for the assessment of malignant SPN. THRIL can regulate the expression of IGF1R through miR-99a, thereby promoting the growth of lung cancer cells and inhibiting apoptosis.

Imbalance towards β-arr2 (-β-arr1/+β-arr2) synergizes with the chemotherapeutic agent, dacarbazine, in promoting melanoma cell toxicity...Combined with other therapeutics, this strategy improves patient responses and outcomes to therapies relying on p53 or IGF1R pathways. Implications: Altogether, β-arrestin system bias downstream IGF1R is an important metastatic melanoma vulnerability that may be conductive for therapeutic benefit.

3. The circIGF1R_ 0001 acts as a potential biomarker for platinum resistance in ovarian cancer and a marker for screening patients who can benefit from PARPi after platinum resistance.

High expression of IGF1R (H-score > 220) in stage III/IV HGSOC patients treated in 1st line platinum derivative-based chemotherapy is a negative prognostic factor.

In biliary malignancies, addition of the immune checkpoint inhibitor to Gemcitabine/Cisplatin has recently become the standard of care in first line treatment, however, the overall survival benefit is moderate in an all-comer population. Our data suggest that an immune suppressive tumor microenvironment associates with suppressive myeloid populations, in addition to high stromal angiogenic activity. Our work thus provides a highly detailed and comprehensive analysis of the iCCA tumor microenvironment and an exploratory analysis of tumor-stromal cell interactions.

Enhanced expression of ASS1 and PYCR1 via IGF1R pathways rewired arginine and proline metabolism, promoting DDP resistance in OSCC under hypoxia. Linsitinib targeting IGF1R signaling may lead to promising combination therapy options for OSCC patients with DDP resistance.

Monensin could suppressed IGF1R expression via increasing IGF1 in colorectal cancer cells. It has the potential to be repurposed as an anti-colorectal cancer agent, but further studies are still required to investigate the detailed mechanisms of monensin underlying its anti-cancer motion.Key MessagesMonensin inhibits the cell proliferation and the migration, induces apoptosis and inhibits cell cycle progression in human colorectal cancer cells.Monensin may exert anti-cancer activity by targeting multiple signaling pathways, including the IGF1R signaling pathway.Monensin has the potential to be repurposed as an anti-colorectal cancer agent.

Here, we used a drug synergy screen that combined a ferroptosis inducer, RSL3, with 240 anti-tumor drugs from the FDA-approved drug library and identified lorlatinib to synergize with RSL3 in melanoma cells. Finally, lorlatinib treatment sensitized melanoma to GPX4 inhibition in preclinical animal models, and melanoma patients with low GPX4 and IGF1R expression in their tumors survived for longer period. Altogether, lorlatinib sensitizes melanoma to ferroptosis by targeting IGF1R-mediated PI3K/AKT/mTOR signaling axis, suggesting that combination with lorlatinib could greatly expand the utility of GPX4 inhibition to melanoma patients with IGF1R-proficient expression.

The present study identified positive association between IGF1R and VDR expression where most of the cases with strong VDR expression displayed strong IGF1R expression. These findings may contribute to current understanding on the role of VDR in BC and its interaction with IGF1R.

Human breast and mouse mammary tumors with reduced IGF1R are associated with upregulation of several pathways necessary for promoting metastasis supporting the conclusion that IGF1R normally helps maintain a metastasis suppressive tumor microenvironment. We further found that reduced IGF1R signaling in tumor epithelial cells dysregulates cadherin expression resulting in reduced cell adhesion.

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).

Upregulated IGF1R expression in one resistant derivative was associated with sensitivity to linsitinib and a profile with upregulation of a YAP/TAZ signature to sensitivity to the YAP inhibitor CA3 in another...Overall, the heterogeneity in resistance mechanisms and commonality of the persister state present a considerable challenge for personalised therapy. Nevertheless, the reversibility of resistance may indicate a benefit from treatment interruptions or re-treatment following disease relapse in some patients.

Surprisingly, however, the absence of IGF1R from ODCs protected against clinical neuroinflammation in the EAE model. Together, our data indicate that IGF-1 signaling is not required for the function and survival of mature ODCs in steady-state and disease.

IGF2 triggers nuclear accumulation of YAP1 and upregulates YAP1 target signatures, however, these effects were abolished by either IGF1R knockdown or inhibition with PPP (picropodophyllin, an IGF1R inhibitor). Using CRC organoid and in vivo studies, we found that co-targeting IGF1R and YAP1 with PPP and VP (verteporfin, a YAP1 inhibitor) enhanced anti-tumor effects compared with PPP treatment alone...In conclusion, this study revealed a novel molecular mechanism by which CAFs promote CRC progression. The findings highlight the translational potential of the IGF2-IGF1R-YAP1 axis as a prognostic biomarker and therapeutic target for CRC.

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

Transfection of ccRCC cells with pre-let-7c-5p significantly inhibited proliferation, migration, invasion, and IGF1R expression. These findings suggest that miRNA dysregulation is involved in ccRCC progression, specifically through invasion, and that let-7c-5p downregulation contributes to the aggressiveness of small ccRCC tumors, in part, through its regulation of IGF1R.

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 immunodeficient mice, stimulation of the HULC-IGF1R pathway promoted tumor metastasis. These data suggest that HULC may be a new epigenetic target for IGF1R axis-targeted therapeutic intervention.

β-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1/IGF1R pathway.

Clinically, patients whose tumors expressed high levels of CD44/IGF1R showed a poor prognosis. This study suggests that IGF1R-dependent CD44 isoform switching confers pancreatic cancer cells to undergo an adaptive change in response to gemcitabine and provides the basis for improved targeted therapy of pancreatic cancer.

Our results demonstrate that IGF1R promotes metastatic tumor initiation and progression in lung TME. Furthermore, our research indicates that IGF1R could be a potential biomarker for early prediction of drug response and clinical evolution in NSCLC patients.

Its regulatory effect may be associated with the miR-98/IGF1R/MEK/ERK signaling pathway. Therefore, LINC01287 has potential for use as a biomarker or therapeutic target for the treatment of BC.

Furthermore, IGF1Rhi Tregs exhibited higher phosphorylation of the mammalian target of the rapamycin complex 1 (mTORC1) in vivo...Furthermore, malignant cells in the tumor nodules induced IGF1R down-regulation in Tregs at the mRNA level. In summary, we identified the heterogeneity of intrahepatic Tregs in HCC which might play significant roles in tumor immunity.

These results indicate that, glucose restricted diet improves lung immune responses of the host and suppresses tumor growth in experimental lung adenocarcinoma. As glucose levels in LUAD patients were negatively correlated to postoperative survival rates, glucose-restricted diet emerges as therapeutic avenue for patients with LUAD.

Additionally, miR-143-3p was validated as a downstream target of circ_0006089, and circ_0006089 could positively regulate IGF1R expression via repressing miR-143-3p. Circ_0006089 is highly expressed in GC, and it promotes the malignancy of GC cells via modulating miR-143-3p/IGF1R axis, suggesting that circ_0006089 may serve as a promising therapeutic target for GC.

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.

Meanwhile, in vivo distribution studies showed that the nanoparticles had a predominant accumulation capacity in liver tissue. These results indicated that clinicians can expect the Mix/CT102 nanocomposite to be very effective in reducing the dose and frequency of clinically administered CT102, thereby reducing the side effects of ASOs.

Besides, metformin has been shown to decrease metastatic events, and enhance the level of metabolic- and insulin-related biomarkers associated with carcinogenesis. Finally, most adverse events following metformin treatment were low-grade GIT toxicities.

Hsa_circ_0003602 acted as a tumor promoter in AML via miR-502-5p/IGF1R axis. Our study provides evidence that hsa_circ_0003602, miR-502-5p, and IGF1R might form a regulatory axis to affect the carcinogenicity of AML cells and provide potential targets for the treatment of AML.

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.

Mechanistically, we revealed that circ_0001459 could sponge miR-6165 and induce the upregulation of its downstream target IGF1R, thus significantly promoting the progression of HCC. Therefore, circ_0001459 could be a new potential therapeutic target for HCC patients.

Ab-miR-NPs not only enhanced the proliferation of sorafenib in cultured HepG2 cells and induced cell apoptosis efficiency, but they also improved the anti-tumor activity in the mouse models. These results indicated that GPC3 antibody-modified PLGA-PLL (polylactic acid-glycolic acetic copolymer grafted hyper-branched polylysine) loaded miR let-7b-5p polymer nanoparticles combined with sorafenib may be a new treatment strategy for HCC resistant to sorafenib.

MALAT1 regulates miR-133a-3p /IGF1R axis. These results show light on the underlying mechanisms of MIRI and provide potential therapeutic targets for MIRI.