In addition, our results showed that pretreatment with linsitinib inhibited IGF-1-induced phosphorylation of IGF-1Rβ at Tyr1135, Akt at Ser473, and ERK in the OFs of patients with TAO. These results indicate that linsitinib inhibits IGF-1-induced cell proliferation and hyaluronic acid secretion in the OFs of TAO patients by suppressing the PI3K/Akt and ERK pathways, validating the use of linsitinib as a novel therapeutic agent for TAO.

P3, N=91, Active, not recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Trial primary completion date: Feb 2025 --> May 2026 | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Dec 2026

P3, N=312, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

In silico, we investigated how mutation of these tyrosines may alter 1248SFYYS1252 conformation, dictating trajectory of the distal CT. We conclude that Tyr1250/1251 phosphorylation confers IGF-1R with unique pro-tumourigenic signalling in a manner that is enhanced by ITGB1.

P1/2, N=253, Recruiting, Fusion Pharmaceuticals Inc. | Trial primary completion date: Jun 2024 --> Jun 2025

Ovarian cancer (OC) remains one of the leading causes of cancer-related mortality among women. Statistical analyses were performed using ordinary one-way or two-way ANOVA, followed by Tukey's or Šídák's multiple comparison tests. While linsitinib shows promise as a therapeutic option for OC, further research is needed to identify agents that could synergize with it to enhance its therapeutic efficacy, like the combination with standard chemotherapy in OC (carboplatin and paclitaxel).

Finally, according to our model and computational drug sensitivity analysis, four small molecule compounds, BMS-754807, SB216763, Doramapimod, and Trametinib, were identified as potential therapeutic agents for patients with MCL. This study provides a prognostic model with ferroptosis-related gene signature for MCL. The results show that the model helps predict prognosis in MCL.

We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.

Our results suggest that the LD-M risk score is an effective prognostic indicator for individualized treatment of LUAD.

Furthermore, genetic ablation of IGF2 or targeted inhibition of the IGF2/IGF1R axis with the inhibitor linsitinib markedly boosted the response to immune checkpoint blockade. Clinically, elevated levels of IGF2 in tumors or plasma correlated with an adverse prognosis and reduced efficacy of anti-programmed death 1 treatment. Together, these results highlight the pivotal role of IGF2 in promoting CAF-mediated immunoevasion, indicating its potential as a biomarker and therapeutic target in immunotherapy.

P1, N=44, Completed, Amgen

Additionally, anti-PD-1/IGF1R treatment increased DC by 34% compared with AEW-541 and 40% with anti-PD-1...RNA-seq data analysis indicated that anti-PD-1/IGF1R led to a more potent immune response, as reflected by altered gene expression levels related to anti-tumor immune response, compared with either treatment alone. These findings provide novel evidence that IGF1R axis inhibition combined with PD-1 blockade may be an effective therapeutic strategy for selected EOC patient populations.

P2, N=36, Active, not recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Recruiting --> Active, not recruiting

P4, N=313, Active, not recruiting, Amgen | Trial completion date: Oct 2025 --> Apr 2026 | Trial primary completion date: Oct 2025 --> Apr 2026

P1/2, N=138, Completed, NantCell, Inc. | Phase classification: P1b/2 --> P1/2

Additionally, TAMs/CXCL1 silence improved paclitaxel chemosensitivity by suppressing autophagy in breast cancer mice xenografts, and clinical studies further linked CXCL1 to IGF1R/HMGB1 signaling, as well as shorter free survival of recurrence. Taken together, these results not only uncover the crucial role of TAMs/CXCL1 signaling in mediating breast cancer chemoresistance through enhancing autophagy, but also shed novel light on the molecular mechanism of IGF1R/STAT3/HMGB1 pathway in regulating autophagy and its impact on cancer prognosis.

IGF1R may serve as a prognostic indicator and a guide for perioperative treatment strategies in early-stage lung cancer. In conclusion, our findings underscore an association between IGF1R expression and poor survival and PD-L1 expression in NSCLC.

We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone...Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed.

P3, N=126, Recruiting, Viridian Therapeutics, Inc.

P3, N=84, Recruiting, Viridian Therapeutics, Inc.

The understanding of up/downstream of the IGF-1/IGF-1R axis provide immense focus on the pathway as a therapeutic target. It is expected within the next decade to determine its potentiality, or lack thereof, for TNBC treatment.

No abstract available

Conversely, hypoxia and the prolyl hydroxylase inhibitor Roxadustat raised TIMAP mRNA and protein levels by inhibiting the BMP9 pathway...Cultured breast cancer E0771 cells released mediators that raised TIMAP expression in endothelial cells, effects that were inhibited by the VEGF inhibitor Sunitinib in conjunction with the IGF-1 inhibitor Picropodophyllin. In the mouse E0771 breast cancer model in vivo, tumor growth and tumor angiogenesis were markedly attenuated in TIMAP deficient, compared to wild-type littermates. These findings indicate that TIMAP plays a critical pro-angiogenic function during tumor angiogenesis in vivo, likely through hypoxia-driven inhibition of the BMP9 pathway and through elaboration of angiogenic growth factors by tumor cells.

BMS-754807 with nab-paclitaxel produced substantially greater antitumor effects by increasing in vivo apoptosis, leading to increased mice survival compared to those of BMS-754807 or nab-paclitaxel monotherapy. Our outcomes support the use of BMS-754807, alone and in combination with nab-paclitaxel, as an efficient and innovative treatment choice for EAC.

P1/2, N=54, Recruiting, ACELYRIN Inc. | N=38 --> 54 | Trial completion date: Oct 2024 --> May 2025 | Trial primary completion date: Oct 2024 --> May 2025

P1/2, N=15, Terminated, NantCell, Inc. | Phase classification: P1b/2 --> P1/2 | N=49 --> 15

The combined over-expression of LIN28B and IGF-1R in patients with colorectal cancer may provide a more powerful predictor for CRC prognosis.

P2, N=36, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

Collectively, these findings suggest that TEAD4 novel transcriptional target RBM8A interacts with EIF4A3 to increase IGF1R and IRS-2 expression and activate PI3K/AKT signaling pathway, thereby further promoting the malignant phenotype of BC cells.

P3, N=80, Recruiting, Amgen | Trial completion date: Sep 2025 --> May 2026

P1/2, N=213, Terminated, NantCell, Inc. | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; Subjects discontinued study

Moreover, circ_0006174 silencing suppressed CRC growth in vivo. Circ_0006174 boosts radioresistance of CRC cells at least partly through upregulating IGF1R expression by sponging miR-940, providing a novel theoretical basis for CRC therapy.

IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

P1, N=37, Completed, Amgen

P1/2, N=89, Terminated, NantCell, Inc. | Phase classification: P1b/2 --> P1/2

P1/2, N=177, Completed, NantBioScience, Inc. | Phase classification: P1b/2 --> P1/2

We reveal a novel targetable kinase fusion oncogene in thyroid cancer which is not incorporated in different thyroid-specific sequencing panels. The integration of IGF1R fusion screening in the next versions of thyroid-specific targeted NGS panels may be beneficial to thyroid cancer patients.

Our results demonstrate that ITGAV is a prognostic biomarker of relapse in cSCCs that would allow improved patient stratification. ITGAV also collaborates with IGF1R to induce EMP in epithelial cancer cells and promotes cSCC progression, revealing a potential therapeutic strategy to block the generation of advanced mesenchymal cSCCs.

P2, N=36, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

In conclusion, KLF15 overexpression promoted the proliferation and metastasis, and suppressed oxidative stress and cell apoptosis of H/R-induced HTR8/SVneo cells through mediating the PI3K/Akt pathway, which may provide a promising target for the treatment of preeclampsia.

Cells were treated with tamoxifen or trastuzumab to examine their role in bidirectional crosstalk. In conclusion, our findings demonstrate the critical role of miR-770-5p in regulating bidirectional crosstalk and overcoming trastuzumab resistance in breast cancer cells. These results highlight the potential of miR-770-5p as a therapeutic target to improve the efficacy of targeted therapies and address resistance mechanisms in breast cancer.

P2, N=10, Terminated, Dana-Farber Cancer Institute | Completed --> Terminated; The study closed early due to discontinuation of ganitumab supply.