linsitinib (ASP7487) / Astellas, Sling Therap - LARVOL DELTA

Cell-based drug screening for personalized treatment of recurrent chordoma (EANO 2026) - "Cell cultures were challenged with increasing concentration of an anti-cancer compound library with promising activity on chordoma (linsitinib, dasatinib, sunitinib, sorafenib, imatinib, rapamycin, erlotinib, lapatinib, pazopanib, regorafenib, lomustine, talidomide, TMZ). Our pipeline for routinely culturing and testing drug sensitivity in chordoma holds a significant translational promise. An effort at treating recurrent chordoma patients after failure of all established treatments with the most effective in vitro drug is underway. Pathway analysis results will inform further research on chordoma."

Chordoma • Oncology

High glucose with insulin signalling blockade promotes cholesterol-sensitive, FAK-dependent UPEC invasion and blunts bladder antimicrobial defence. (PubMed, Biochem Biophys Res Commun) - "In 5637 bladder epithelial cells, OSI-906 reduced AKT phosphorylation and, under high-glucose conditions, increased UPEC adhesion and intracellular recovery...In db/db mice, increased bladder bacterial burden was accompanied by reduced early infection-associated host-defence responses compared with db/+ controls. Together, these findings suggest that high glucose, combined with insulin signalling blockade, reorganises the urothelial membrane toward a more accessible, cholesterol-sensitive state that favours FAK-dependent UPEC invasion while weakening bladder antimicrobial defence."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Nephrology

A primary hepatopancreatic cell platform enables cellular dissection of glucose metabolism and endocrine-metabolic regulation in Litopenaeus vannamei. (PubMed, Front Endocrinol (Lausanne)) - "Linsitinib treatment substantially blunted glucose responsiveness and shifted the transcriptional profile toward impaired glucose utilization...Collectively, this study establishes a controllable and expandable primary hepatopancreatic cell platform for dissecting nutrient sensing, glucose metabolic homeostasis, and endocrine-metabolic regulation in L. vannamei. This system provides a valuable cellular tool for crustacean endocrinology and metabolism research and offers a useful framework for future functional studies in economically important crustacean species."

Journal • Endocrine Disorders

Genetic alterations and targeted therapies in salivary gland neoplasms. (PubMed, Sci Prog) - "For instance, pleomorphic adenomas often have PLAG1 overexpression and FGFR1 fusions, activating the IGF and WNT signaling pathways; linsitinib, a dual IGF1R and tyrosine kinase inhibitor, has demonstrated antitumor activity in other malignancies and may hold potential in this context...Further research is needed to validate these findings in clinical trials. Overall, integrating molecular diagnostics with pathway-specific targeted therapies may enhance outcomes and expand treatment options for patients with SGNs."

Journal • Review • Oncology • Salivary Gland Cancer • Solid Tumor • FGFR1 • HER-2 • PLAG1

Sling Therapeutics…announced the first patients have been dosed in the global Phase 3 ORBIT pivotal trial, a global, randomized, double-masked, placebo-controlled study evaluating the efficacy and safety of linsitinib…in adults with moderate to severe active thyroid eye disease (TED) (Businesswire) - "ORBIT is expected to enroll approximately 130 participants, randomized 1:1 to receive oral linsitinib 150 mg or placebo twice daily for 24 weeks. The primary endpoint is the proportion of proptosis responders at Week 24, defined as participants achieving a reduction of at least 2 mm in proptosis in the study eye without a corresponding worsening in the fellow eye."

Trial status • Thyroid Eye Disease

Insulin-like Growth Factor Signaling Promotes Corneal Myofibroblast Survival and Sustains Corneal Fibrosis. (PubMed, Int J Mol Sci) - "In this study, we investigated the role of the insulin-like growth factor (IGF) signaling axis in corneal myofibroblast survival and evaluated the therapeutic potential of linsitinib, a dual IGF-1 receptor (IGF-1R)/insulin receptor (INSR) inhibitor...These findings identify the IGF axis as a critical regulator of corneal myofibroblast survival and suggest that persistent fibrosis is maintained, in part, by IGF-dependent resistance to apoptosis. Targeting survival pathways rather than myofibroblast differentiation may represent a novel therapeutic strategy for the treatment of corneal fibrosis."

Journal • Fibrosis • Immunology • IGF1 • IGF2 • IR • TGFB1

LIDS: A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED) (clinicaltrials.gov) - P2/3 | N=90 | Completed | Sponsor: Sling Therapeutics, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2026 ➔ Sep 2025

Trial completion • Trial completion date • Endocrine Disorders • Ophthalmology • Thyroid Eye Disease

FECH, a novel metabolic target influencing CAR T-cell phenotype and function. (PubMed, Biomark Res) - "We previously demonstrated the therapeutic benefit of combining the dual insulin-like growth factor 1 receptor/insulin receptor (IGF1R/IR) inhibitor linsitinib (LIN) with third-generation GD2.CAR T cells in diffuse intrinsic pontine glioma, where LIN induced tumor cell death and modulated the CAR T-cell phenotype...Collectively, these data reveal a dual mechanism of action for LIN, combining direct tumor cell cytotoxicity with metabolic reprogramming of CAR T cells linked to heme biosynthesis. These findings identify heme metabolism as regulator of CAR T-cell phenotype and function and support further investigation of FECH to enhance therapeutic efficacy in NB and beyond."

Journal • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • IR

ORBIT: Study to Assess Linsitinib in Participants With Moderate to Severe Active Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=130 | Recruiting | Sponsor: Sling Therapeutics, Inc.

New P3 trial • Ophthalmology • Thyroid Eye Disease

Synergistic Profiling of Programmed Cell Death and Immune Responses Identifies a Novel Prognostic Index for Cervical Cancer. (PubMed, ACS Omega) - "Profiling of drug susceptibility revealed that the high-risk cohort of patients showed resistance to rapamycin and idelalisib but were sensitive to thapsigargin and linsitinib. Overall, the ICDI shows strong potential as a prognostic marker for forecasting clinical outcomes and could facilitate personalized treatment strategies for CC patients."

Journal • Cervical Cancer • Oncology • Solid Tumor • FADD • MUC4

Endothelial insulin-like growth factor 1 receptor-targeted vessel normalization potentiates neuroendocrine cancer immunotherapy. (PubMed, Trends Pharmacol Sci) - "identified a blood-brain barrier-like vascular gate that mediates immune exclusion and immunotherapy resistance in small-cell lung cancer. Targeting this barrier with OSI-906 enhances CD8+ T-cell infiltration and immunotherapy efficacy."

Journal • Endocrine Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD8

Metabolic rate-limiting enzyme-associated genes as novel biomarkers for prognosis and treatment response in lung adenocarcinoma. (PubMed, Comput Methods Biomech Biomed Engin) - "Drug sensitivity analysis identified multiple promising candidate agents (Linsitinib, Momelotinib, and GDC-0152). Collectively, metabolic rate-limiting enzyme-related genes can be promising LUAS prognostic biomarkers. The risk model is expected to provide reliable references for LUAD prognostic assessment and individualized treatment."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mapping Resistance and Pre-Sensitization to FLT3 Inhibitors in Acute Myeloid Leukemia Using Single-Cell Lineage Tracing (EACR 2026) - "The objective of this study was to elucidate mechanisms underlying primed resistance to FLT3 inhibitors driven by intrinsic transcriptional heterogeneity and to identify novel agents capable of pre-sensitizing AML cells to FLT3-targeted therapy.Material and To identify pre-existing resistant states to FLT3 inhibitors midostaurin and quizartinib, we applied our single-cell lineage-tracing platform, ReSisTrace, in an FLT3-ITD–positive MOLM-13 AML cell line. Our lineage-tracing approach enables the identification of transcriptional states that precede primed resistance to FLT3 inhibitors in FLT3-ITD–mutated AML. Targeting the pre-resistance gene GSPT1 with the molecular degrader CC-90009 produces robust synergistic effects with FLT3 inhibitors both in vitro and in vivo, highlighting a promising strategy to enhance therapeutic efficacy in FLT3-ITD–positive AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Targeted Protein Degradation • CRBN • FLT3 • GSPT1 • IR

Integrative analysis of lncRNAs associated with disulfidptosis-related genes for prognostic risk evaluation and tumor immune microenvironment assessment in laryngeal squamous cell carcinoma. (PubMed, Hum Cell) - "Exploratory in silico drug-response analyses identified differential predicted responses to entinostat, linsitinib, and VE-822 according to risk status and DUBR expression. This internally validated signature may support exploratory prognostic risk stratification of LSCC within the analyzed TCGA-derived cohort and may highlight DUBR as a candidate molecule for further biological investigation. Further validation in independent external cohorts and dedicated disulfidptosis functional assays is required before these findings can be considered generalizable."

Journal • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • METTL3 • TLN1

Identification of MMP14 and FOS as key regulators of vascular smooth muscle cell senescence in diabetic kidney disease: A combined bioinformatics and experimental study. (PubMed, Arch Gerontol Geriatr) - "MMP14 and FOS function as crucial modulators of VSMC senescence in DKD, presenting diagnostic and therapeutic opportunities. The characterized regulatory circuits and identified pharmaceutical agents establish a foundation for precision interventions in DKD management."

Journal • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • CDKN1A • MIR181A1 • MMP14 • NEAT1 • SPP1

A blood-brain barrier-like vascular gate limits immunotherapy efficacy in neuroendocrine cancers. (PubMed, Cell) - "IGFBP5 knockout or treatment with the IGF1R inhibitor OSI-906 enhances CD8+ T cell infiltration and synergizes with anti-PD1 therapy. Furthermore, this ASCL1-IGFBP5-IGF1R axis and the BVG are conserved across multiple neuroendocrine cancers (NECs). Our findings reveal a previously unrecognized vascular gate in NECs and propose novel therapeutic strategies to enhance immunotherapy efficacy in these recalcitrant cancers."

Journal • Endocrine Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • CD8 • IGF1 • IGFBP5

Investigation of Linsitininb on Nitric Oxide Production in Lipopolysaccharide-induced RAW264.7 Macrophages for Ocular Surface and Orbital Inflammation (ARVO 2026) - "These findings, indicate that linsitinib exerts potent anti-inflammatory and immunomodulatory effects on macrophage activation. Future research in understanding the attenuation in linsitinib in ocular surface and orbital inflammation may provide useful clinical insights."

Ocular Inflammation • Ophthalmology • IR

Integrative pathway analysis of I-SPY2 HER2+ breast cancers reveals drug-repurposing opportunities (AACR 2026) - "Growth-factor/RTK bypass (PI3K/AKT) and DNA repair & oxidative stress defense were strongly upregulated in non-responders within BP-HER2, revealing actionable nodes involving PI3K/AKT (alpelisib, capivasertib), IGF1R (linsitinib), MET (crizotinib, capmatinib), and DNA repair (PARP inhibitors). Notably, metabolic rewiring and lipid homeostasis—targetable by vismodegib and sonidegib—were upregulated in non-responders across both BP subtypes, reflecting a shared metabolic vulnerability. Luminal biology-linked transcriptional programs may persist within the HER2+ BP-HER2 subtype and contribute to resistance... Luminal biology-linked transcriptional programs may persist within the HER2+ BP-HER2 subtype and contribute to resistance. BP-HER2 non-responders exhibit coordinated activation of RTK-bypass and DNA repair pathways, exposing therapeutic vulnerabilities targetable by existing agents. Furthermore, targeting lipid metabolic reprogramming alongside anti-HER2 therapy..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Non-animal platforms using ex-vivo human tissue and live-cell biosensors enable functional drug testing in renal cell carcinoma (AACR 2026) - "Treatment groups included: a) cabozantinib (cabo) alone, b) cabo with cemiplimab (cemi, a PD-1 inhibitor), c) cemi with fianlimab (fin, a LAG-3 inhibitor)...Cells were plated on biosensor-compatible microplates and treated with metabolic inhibitors (2-DG, oligomycin) and pharmacological targeted drugs relevant to RCC [(PI103- PI3K/mTOR inhibitor), sunitinib and cabozantinib (tyrosine kinase inhibitors), and linsitinib (IGF1R inhibitor)]... This integrated, fully non-animal strategy overcomes key limitations of animal models by combining preserved human tumor microenvironments with high-resolution metabolic biosensing. Together, these platforms enable rapid and mechanism-based profiling of therapeutic vulnerabilities in RCC."

Preclinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AMPK • HIF1A • LAG3

Multi-Omics and Machine Learning Analyses Reveal PIK3CG, PRKCD, and TRIM22 as Potential Markers of Poor Prognosis and Immune Activation in Glioblastoma. (PubMed, J Korean Med Sci) - "This study identifies PIK3CG, PRKCD, and TRIM22 as potential biomarkers and therapeutic targets in IDH-wildtype GBM. Their paradoxical association with poor survival and immune activation may inform personalized treatment strategies that combine conventional chemotherapy with immune-based therapies. While our findings are robust across both mixed and IDH-wildtype-focused cohorts, further mechanistic validation is warranted."

Biomarker • IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CD4 • CD8 • PD-L1 • PIK3CG • TRIM22

Combination therapy with AKT and MEK inhibitors is effective in patient-derived models of adrenocortical carcinoma (AACR 2026) - "Surprisingly, we found that linsitinib completely downregulated phospho-AKT suggesting AKT is a key downstream pathway of IGF2-IGFR1 in ACC...In vivo, the 2-drug AKT and MEK inhibitor combination demonstrated greater anti-tumor activity than either agent alone in an ACC cell-line xenograft and two chemoresistant ACC patient-derived xenograft models. Our results demonstrate a novel, active drug combination in refractory ACC that warrants clinical investigation."

Clinical • Combination therapy • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • IGF1 • IGF2 • MAP2K1

Insulin-like growth factor 1 by lung fibroblasts from patients with idiopathic pulmonary fibrosis contributes to the development of fibrosis. (PubMed, Respir Investig) - "These results suggest that IGF-1 amplifies TGF-β-driven profibrotic responses and may represent a potential therapeutic target for IPF."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • IGF1 • TGFB1

Frequent copy number gain of MCL1 is a therapeutic target for osteosarcoma (AACR 2024) - "The treatment for OS that combines surgery with chemotherapy, which consists of a four-drug combination of adriamycin (DOX), cisplatin (CDDP), high-dose methotrexate (MTX), and ifosfamide, was established in 1970s, and it is still used as a standard therapy...Herein, to explore the characteristic vulnerability in OS, molecular targeted drugs were screened against OS cell lines and patient-derived cells; obatoclax, a pan-BH3 mimetic, and a concomitant drug that enhances obatoclax-induced apoptosis, OSI906, a dual inhibitor of IGF1R and IR, were found...Thus, we elucidated the mechanism of action of drugs and their potential as a novel therapeutic strategy for approximately 50% of patients with OS. Moreover, a FISH analysis that can detect copy number gains of MCL1 in FFPE specimens from patients with OS was established to stratify patients eligible for this therapy."

IO biomarker • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BCL2 • BCL2L1 • PIP5K1A

Targeting CXCR4 via the small molecule inhibitor NMX1 as a therapeutic strategy to treat high-risk malignancies (AACR 2024) - "In animal models of breast cancer, NMX1 effectively prevented tumor growth and metastasis, while also protecting from doxorubicin-induced cardiotoxicity. Our study shows antitumor activity by NMX1 through inhibition of CXCR4, IL-11, and mTOR signaling, providing an effective therapeutic strategy for high-risk and refractory malignancies. Preclinical data on feasible drug combinations and biological correlates of activity support development of early phase clinical studies involving NMX1."

Breast Cancer • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Sarcoma • Solid Tumor • CXCL12 • CXCR4 • MET

Genomic amplification of MCL1 as a therapeutic target for osteosarcoma (AACR 2025) - "The treatment for OS that combines surgery with chemotherapy, which consists of a four-drug combination of doxorubicin (DOX), cisplatin (CDDP), high-dose methotrexate (MTX), and ifosfamide, was established in 1970s, and it is still used as a standard therapy...Additionally, the combination of MIK665 with IGF-1R inhibitors, including OSI906, AEW541, and AZD3463, induced synergistic cell death by overcoming drug tolerance conferred by the activation of IGF signaling in OS cells...Moreover, the combination therapy of AZD5991 with OSI906 also reduced tumor growth in the NOS-10 xenograft model. These results suggest that genomic amplification of MCL1 in the 1q21.2-3 region, observed in nearly half of OS patients, may act as a predictive biomarker for combination therapy with an Mcl-1 inhibitor and an IGF1-R inhibitor."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IGF1 • NOS1 • PIP5K1A