^
2ms
Inhibition of Insulin-like Growth Factor 1 Receptor/Insulin Receptor Signaling by Small-Molecule Inhibitor BMS-754807 Leads to Improved Survival in Experimental Esophageal Adenocarcinoma. (PubMed, Cancers (Basel))
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.
Journal
|
IR (Insulin receptor)
|
albumin-bound paclitaxel • BMS-754807
4ms
Dissecting gastric cancer heterogeneity and exploring therapeutic strategies using bulk and single-cell transcriptomic analysis and experimental validation of tumor microenvironment and metabolic interplay. (PubMed, Front Pharmacol)
Despite resistance to immunotherapy, the high-risk group showed sensitivity to molecular targeted agents directed at IGF-1R (BMS-754807) and the PI3K-mTOR pathways (AZD8186, AZD8055). This study unveils the intricate interplay between TME and metabolic pathways in gastric cancer, offering potential for enhanced diagnosis, patient stratification, and personalized treatment. Understanding molecular features in each subtype enriches our comprehension of gastric cancer heterogeneity and potential therapeutic targets.
Journal • IO biomarker
|
MSI (Microsatellite instability) • CD36 (thrombospondin receptor) • KYNU (Kynureninase)
|
AZD8055 • BMS-754807 • AZD8186
6ms
Exogenous Metabolic Modulators Improve Response to Carboplatin in Triple-Negative Breast Cancer. (PubMed, Cells)
Thus, we tested whether inhibition of insulin receptor/insulin-like growth factor 1 receptor with the drug BMS-754807 and/or lysosomal disruption with hydroxychloroquine (HCQ) could sensitize TNBC cells to the chemotherapy drug carboplatin. Additionally, we demonstrate the lack of overt in vivo toxicity with our combination regimens and, therefore, propose that metabolic targeting of TNBC may be a safe and effective strategy to increase sensitivity to chemotherapy. Thus, we conclude that the use of exogenous metabolic modulators, such as BMS-754807 or HCQ, in combination with chemotherapy warrants additional study as a strategy to improve therapeutic responses in women with TNBC.
Journal
|
IR (Insulin receptor)
|
carboplatin • BMS-754807 • hydroxychloroquine
7ms
Pan-cancer analysis of prognostic and immunological role of IL4I1 in human tumors: a bulk omics research and single cell sequencing validation. (PubMed, Discov Oncol)
IL4I1 may play a role as promoter of cancer and prognostic indicator in patients. High expression of IL4I1 is associated with the state of tumor immunosuppression and may contribute to tumor-associated macrophage invasion. Therefore, IL4I1 may be a new therapeutic target for the treatment and prognosis of patients with cancer.
Journal • Pan tumor
|
IL4 (Interleukin 4) • IL4I1 (Interleukin 4 Induced 1)
|
docetaxel • temozolomide • BMS-754807
10ms
Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes. (PubMed, World J Clin Oncol)
Our findings emphasizes the role of disulfidptosis in regulating tumor development, therapeutic response, and patient survival in CRC patients. For the clinical treatment of CRC, these important LncRNAs could serve as viable therapeutic targets.
Journal • IO biomarker
|
IL17A (Interleukin 17A)
|
bortezomib • epirubicin • BMS-754807 • Vumon (teniposide)
10ms
A ten long noncoding RNA-based prognostic risk model construction and mechanism study in the basal-like immune-suppressed subtype of triple-negative breast cancer. (PubMed, Transl Cancer Res)
In addition, drug sensitivity analysis identified 3 compounds, including BMS-754807, cytochalasin b, and linifanib, that could have a potential therapeutic effect on patients with the BLIS subtype. The risk prognosis model showed good prognostic value for the BLIS subtype patients, and the ten lncRNAs may be potential therapeutic targets.
Journal
|
AR (Androgen receptor) • FZD10 (Frizzled Class Receptor 10) • DIO3OS (DIO3 Opposite Strand Upstream RNA)
|
BMS-754807 • linifanib (ABT-869)
1year
Prognostic and Predictive Utility of GPD1L in Human Hepatocellular Carcinoma. (PubMed, Int J Mol Sci)
Moreover, we demonstrated an inverse correlation between GPD1L expression and therapeutic response for three therapeutic agents (PF-562271, Linsitinib, and BMS-754807), highlighting its potential as a predictive biomarker for HCC treatment outcomes. These data provide insights into the prognostic significance, molecular characteristics, and predictive potential of GPD1L in HCC.
Journal
|
BMS-754807 • linsitinib (ASP7487) • benzesulfonate (PF-562271)
1year
Regulation of IGF1R by MicroRNA-15b Contributes to the Anticancer Effects of Calorie Restriction in a Murine C3-TAg Model of Triple-Negative Breast Cancer. (PubMed, Cancers (Basel))
These effects were reversed by the pharmacological inhibition of IGFR with BMS754807...Our findings suggest that CR in association with reduced IGF1 levels could upregulate miR-15b to downregulate Igf1r and contribute to the anticancer effects of CR. Thus, miR-15b may be a therapeutic target for mimicking the beneficial effects of CR against TNBC.
Preclinical • Journal
|
IGF1 (Insulin-like growth factor 1) • MIR199A1 (MicroRNA 199a-1) • MIR199A (MicroRNA 199a) • MIR15B (MicroRNA 15b) • MIR486-1 (MicroRNA 486-1)
|
BMS-754807
1year
Establishment of a large-scale patient-derived high-risk colorectal adenoma organoid biobank for high-throughput and high-content drug screening. (PubMed, BMC Med)
This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on the prevention of colorectal cancer.
Preclinical • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • WNT3 (Wnt Family Member 3)
|
Farydak (panobinostat) • BMS-754807 • metformin • AT9283
1year
Three candidate anticancer drugs were repositioned by integrative analysis of the transcriptomes of species with different regenerative abilities after injury. (PubMed, Comput Biol Chem)
Based on these gene signatures, we investigated 3 small compounds, namely cucurbitacin I, BMS-754807, and PHA-793887 as potential candidates for the treatment of cancer. Future studies on the mechanisms associated with the revealed gene signatures and anticancer effects of these three small compunds would allow scientists to develop therapeutic approaches to combat cancer. This research contributes to the evaluation of mechanisms and gene signatures that either limit or cause cancer, and to the development of new cancer therapies by establishing a link between regeneration and carcinogenesis.
Journal
|
BMS-754807 • cucurbitacin I (JSI-124) • PHA 793887
over1year
HIGH-THROUGHPUT AND HIGH-CONTENT DRUG SCREENING ON A LARGE-SCALE PATIENT-DERIVED HIGH-RISK COLORECTAL ADENOMA ORGANOID PLATFORM (UEGW 2023)
Four drugs including metformin, BMS754807, Panobinostat, and AT9283 were screened out as potential hits with generally consistent inhibitory efficacy on HRCA-PDOs. This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on prevention of colorectal cancer.
Clinical
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • WNT3 (Wnt Family Member 3)
|
Farydak (panobinostat) • BMS-754807 • metformin • AT9283
over1year
Dasatinib in combination with BMS-754807 induce synergistic cytotoxicity in lung cancer cells through inhibiting lung cancer cell growth, and inducing autophagy as well as cell cycle arrest at the G1 phase. (PubMed, Invest New Drugs)
Furthermore, dasatinib (18 mg/kg) in combination with BMS-754807 (18 mg/kg) inhibited the growth of tumors in NCI-H3255 xenografts without changing the bodyweight. Overall, our results suggest that dasatinib in combination with BMS-754807 inhibits the lung cancer cell proliferation in vitro and tumor growth in vitro, which indicates promising evidence for the application of the drug combination in lung cancer therapy.
Journal • Combination therapy
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • SQSTM1 (Sequestosome 1) • IR (Insulin receptor) • BECN1 (Beclin 1)
|
CCND1 expression • CDK6 expression
|
dasatinib • BMS-754807
over1year
A Deep Learning Approach for Prognostic Evaluation of Lung Adenocarcinoma Based on Cuproptosis-Related Genes. (PubMed, Biomedicines)
Furthermore, our model provided personalized survival probability predictions with a concordance index of 0.795 and identified the drug candidate BMS-754807 as a potentially sensitive treatment option for lung adenocarcinoma. In summary, we presented a deep neural network prognostic model for lung adenocarcinoma, based on nine cuproptosis-related genes, which offers independent prognostic capabilities. This model can be used for personalized predictions of patient survival and the identification of potential therapeutic agents for lung adenocarcinoma, which may ultimately improve patient outcomes.
Journal • Tumor mutational burden
|
TMB (Tumor Mutational Burden)
|
BMS-754807
over2years
SS18-SSX drives CREB activation in synovial sarcoma. (PubMed, Cell Oncol (Dordr))
In conclusion, our data underline an essential role of CREB in SySa tumorigenesis and provides evidence for molecular targeted therapies.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • BCL2L1 (BCL2-like 1) • PCNA (Proliferating cell nuclear antigen) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
|
SS18-SSX fusion
|
BMS-754807 • bisindolylmaleimide IX (RO-31-8220)
over2years
Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner. (PubMed, Sci Rep)
In line with this, 10 Gy SD cells were more sensitive to target inhibition with Capivasertib or Ipatasertib (AKTi), BMS-754807 (IGF-1Ri), or Foretinib (VEGFR2/METi), but less sensitive to Panobinostat or Vorinostat (HDACi). In summary, understanding the molecular short- and long-term changes after irradiation can aid in optimizing the efficacy of multimodal radiation oncology in combination with post-irradiation molecularly-targeted drug treatment and improving the outcome of prostate cancer patients.
Journal
|
KDR (Kinase insert domain receptor)
|
KDR expression
|
Truqap (capivasertib) • ipatasertib (RG7440) • Zolinza (vorinostat) • Farydak (panobinostat) • BMS-754807 • foretinib (GSK1363089)
over2years
IGF-1R nuclear import and recruitment to chromatin involves both alpha and beta subunits. (PubMed, Discov Oncol)
Using prostate cancer cell lines DU145 and 22Rv1 we detected nuclear α- and β-subunits, with increase in nuclear signal upon IGF-treatment and reduction in response to IGF-1R inhibitor BMS-754807...Finally, we detected recruitment of both subunits to regulatory regions of chromatin, including the promoter of the oncogene JUN, that we previously identified in ChIP-seq as sites of IGF-1Rβ enrichment. These data confirm the cell surface origin of nuclear IGF-1R, suggest the presence of nuclear αβ complexes and reveal that both IGF-1Rα- and β-subunits contribute to pro-tumorigenic functions of nuclear IGF-1R.
Journal
|
JUN (Jun proto-oncogene)
|
BMS-754807
almost3years
IGF1R/IR Mediates Resistance to BRAF and MEK Inhibitors in BRAF-Mutant Melanoma. (PubMed, Cancers (Basel))
The combination of dabrafenib, trametinib, and BMS-754807 treatment reduced in vivo xenograft tumor growth. Examining the role of IGF1R and IR in mediating resistance to BRAF and MEK inhibitors will expand possible treatment options to aid in long-term success for BRAF-mutant melanoma patients.
Journal
|
IGF1R (Insulin-like growth factor 1 receptor) • IR (Insulin receptor)
|
BRAF mutation
|
Mekinist (trametinib) • Tafinlar (dabrafenib) • BMS-754807
3years
Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer. (PubMed, Front Pharmacol)
In addition, we observed that flavopiridol alone or in combination with the chemotherapeutic agent nanoparticle albumin-bound paclitaxel (NPT) or in combinations with the targeted agent BMS-754807 significantly inhibited esophageal cancer cell proliferation and subcutaneous xenograft tumor growth while significantly enhancing overall mice survival. These results indicate that aggressive esophageal cancer cells with elevated c-Myc expression are sensitive to the CDK inhibitor flavopiridol, and that flavopiridol alone or in combination can be a potential therapy for c-Myc overexpressing esophageal cancer.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
MYC amplification • MYC overexpression • MYC expression
|
albumin-bound paclitaxel • BMS-754807 • alvocidib (DSP-2033)
over3years
IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK. (PubMed, Sci Rep)
Focal Adhesion Kinase (FAK) and Paxillin phosphorylation were decreased as early as 15 min after treatment, and treatment with a FAK inhibitor, PF-562,271, was sufficient to decrease viability in vitro. Most strikingly, treatment with BMS754807 and dasatinib, or a FAK inhibitor alone, significantly increased cleaved-PARP in human ex-vivo HNSCC patient tissues demonstrating a potential clinical utility for targeting FAK or the combined targeting of the IGF1R with Src. This ex-vivo result further confirms FAK as a vital signaling node of this combinatorial treatment and demonstrates therapeutic potential for targeting FAK in HNSCC patients.
Journal
|
PXN (Paxillin)
|
dasatinib • BMS-754807 • benzesulfonate (PF-562271)
over3years
IGF-1R nuclear import and recruitment to chromatin involves both alpha and beta subunits. (PubMed, Discov Oncol)
Using prostate cancer cell lines DU145 and 22Rv1 we detected nuclear α- and β-subunits, with increase in nuclear signal upon IGF-treatment and reduction in response to IGF-1R inhibitor BMS-754807...These data confirm the cell surface origin of nuclear IGF-1R, suggest the presence of nuclear αβ complexes and reveal that both IGF-1Rα- and β-subunits contribute to pro-tumorigenic functions of nuclear IGF-1R. The online version contains supplementary material available at 10.1007/s12672-021-00407-8.
Journal
|
JUN (Jun proto-oncogene)
|
BMS-754807
over3years
[VIRTUAL] Insulin-like growth factor-2 a potential target for screening and treatment in patients with triple negative breast cancer (AACR 2021)
This data suggest that IGF2 is a potential biological marker for breast cancer disparities and that targeting receptors of IGF2 with drugs such as BMS-754807 could provide additional treatment options in combination with current therapies, thus reducing TNBC progression and ultimately improving patient outcomes. [Funded by NIH U54 143931 Cancer Center Partnership and CBCRP]
Clinical
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IGF2 (Insulin-like growth factor 2) • IR (Insulin receptor)
|
BMS-754807
over3years
[VIRTUAL] Anticancer effects of calorie restriction in a murine C3-TAg model of triple-negative breast cancer: the role of miR-15b (AACR 2021)
To mimic CR in vitro, and to test the effects of miRNA manipulation, the C3-Tag series of TNBC cell lines were treated (separately and in combination) with serum restriction, BMS754807 (inhibitor of IGF1-R), and various levels of recombinant IGF-1 as well as manipulated levels of miRNA’s associated with IGF-1/mTOR signaling...Together these findings suggest that reduced circulating IGF-1 levels in response to CR leads to the upregulation of miR-15b, which correspondingly targets and downregulates IGF-1R, both at the mRNA and protein levels. This combination of reduced IGF-1 ligand and miR-15b-induced IGF-1R downregulation contributes to the potent anticancer effects of CR and reveals potential targets for pharmacologically mimicking those effects.
Preclinical
|
IGF1 (Insulin-like growth factor 1) • MIR15B (MicroRNA 15b)
|
BMS-754807
almost4years
Depletion of insulin-like growth factor 1 receptor increases radiosensitivity in colorectal cancer. (PubMed, J Gastrointest Oncol)
Two radio-resistant colorectal cancer cell lines, SW480 and HT29, were selected for in vitro studies, and the involvement of the IGF1R in their radiation resistance was elucidated by suppressing its expression through a targeted siRNA and through the use of a specific IGF1R inhibitor, BMS-754807...This study supports the notion that the radiosensitivity of radiation-resistant colorectal cancer cells can be enhanced by directly targeting IGF1R expression or activity. Ultimately, the combination of radiotherapy with IGF1R targeted inhibitors could potentially increase its effectiveness in the treatment of advanced colorectal cancer.
Journal
|
IGF1R (Insulin-like growth factor 1 receptor)
|
IGF1R expression
|
BMS-754807
almost4years
Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines. (PubMed, Cancers (Basel))
Taken together, our results are indicative that BMS mainly acts through off-target effects exerted on other protein kinases. Given that BMS exhibits a potent antiproliferative effect, we believe that this compound could be useful for the treatment of different types of tumors independently of their IGF-1R activation status.
Preclinical • Journal
|
IGF1R (Insulin-like growth factor 1 receptor)
|
BMS-754807 • linsitinib (ASP7487)
4years
Stratification and prediction of drug synergy based on target functional similarity. (PubMed, NPJ Syst Biol Appl)
In addition, we experimentally validated predicted synergy of the BRAF/insulin receptor combination (Dabrafenib/BMS-754807) in 48 colorectal cancer cell lines. We anticipate that our approaches can be used for prioritization of drug combinations in large scale screenings, and to maximize the efficacy of drugs already known to induce synergy, ultimately enabling patient stratification.
Journal
|
BRAF (B-raf proto-oncogene) • IR (Insulin receptor)
|
Tafinlar (dabrafenib) • BMS-754807
4years
Metformin and an insulin/IGF-1 receptor inhibitor are synergistic in blocking growth of triple-negative breast cancer. (PubMed, Breast Cancer Res Treat)
We conclude that the combination of metformin and BMS-754807 is more effective than either drug alone in inhibiting cell proliferation in the majority of TNBC cell lines, and that one important mechanism may be suppression of SCF and subsequent stabilization of the cell cycle inhibitor p27. This combination treatment may represent an effective targeted therapy for a significant subset of TNBC cases and should be further evaluated.
Journal
|
IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1) • IR (Insulin receptor)
|
BMS-754807 • metformin
4years
IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas. (PubMed, Signal Transduct Target Ther)
Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. Furthermore, the combination of BMS-754807 and U0126 efficiently decreased the cell viability and increased cleaved caspase 3 and apoptosis in vitro and in vivo. Our data suggest that the treatment of colon tumor cells with IGF-1R inhibitors stimulates p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • CASP3 (Caspase 3) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • RPS6 (Ribosomal Protein S6)
|
PIK3CA mutation
|
BMS-754807 • U0126 • GSK 1838705A
4years
Targeting TSLP-induced tyrosine kinase signaling pathways in CRLF2-rearranged Ph-like ALL. (PubMed, Mol Cancer Res)
Fixed-ratio combination cytotoxicity assays using the tyrosine kinase inhibitors BMS-754807 and ponatinib that target IGF1R and FGFR1, respectively, revealed strong synergy against both cell line and patient-derived xenograft (PDX) models of CRLF2r Ph-like ALL. While this study identified potential new targets in CRLF2r Ph-like ALL, it also highlights that in vivo validation of synergistic drug interactions is essential. Implications: Quantitative phosphotyrosine profiling identified potential therapeutic targets for high-risk CRLF2-rearranged Ph-like ALL.
Journal
|
FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IGF1R (Insulin-like growth factor 1 receptor) • JAK1 (Janus Kinase 1) • FGF (Fibroblast Growth Factor)
|
CRLF2 rearrangement
|
Iclusig (ponatinib) • BMS-754807
over4years
[VIRTUAL] Combination of insulin-like growth factor-1 receptor/insulin receptor (IGF1R/IR) antagonist with anti-PD-L1 antibody blocks triple-negative breast cancer (TNBC) progression (AACR-II 2020)
Combination treatment of BMS-754807 (IGF1R/IR) with NVP-AEW541 (IGF1R inhibitor) reduced proliferation of human MDA-MB-231, BT549, HCC1937 and murine 4T1 TNBC cells in vitro (P<0.001). Use of immunotherapy is a promising management option for a subset of TNBC patients, and combination treatments using IGF1R antagonists with immune checkpoint inhibitor may constitute a new treatment strategy to combat this deadly disease. &lsqb;Funding by NCI U54 CA1433930; California Breast Cancer Research Program; UCLA Jonsson
Late-breaking abstract • PD(L)-1 Biomarker • IO biomarker
|
IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2) • IR (Insulin receptor)
|
MSLN positive
|
BMS-754807 • NVP-AEW541
over4years
Loss of HAT1 expression confers BRAFV600E inhibitor resistance to melanoma cells by activating MAPK signaling via IGF1R. (PubMed, Oncogenesis)
We showed that both MAPK and IGF1R pathway inhibition, using the ERK inhibitor SCH772984 and the IGF1R inhibitor BMS-754807, respectively, restored BRAFi sensitivity in melanoma cells lacking HAT1. Collectively, we show that the loss of HAT1 expression confers acquired BRAFi resistance by activating the MAPK signaling pathway via IGF1R.
Journal
|
BRAF (B-raf proto-oncogene) • IGF1R (Insulin-like growth factor 1 receptor)
|
BRAF V600E • BRAF mutation
|
SCH772984 • BMS-754807