Cilcane (cilengitide) / Iceni Pharma - LARVOL DELTA

Anticancer Peptides: Design Principles, Translational Bottlenecks, and Emerging Opportunities. (PubMed, Molecules) - "Representative clinical programs-including the oncolytic peptide LTX-315, the cell-penetrating peptide p28, the stapled peptide ALRN-6924, the tumor-penetrating peptide CEND-1, and the cyclic integrin inhibitor cilengitide-illustrate both the reach of peptide pharmacology and recurrent causes of attrition. We propose a developability-centered workflow that links mechanism, route of administration, pharmacokinetics, pharmacodynamics, biomarker strategy, formulation and chemistry, manufacturing, and controls from the beginning of discovery. For the next generation of ACP development, the most credible opportunities lie in route-matched local or regional therapy, mechanism-based combinations, experimentally constrained artificial intelligence, and peptide-enabled delivery systems supported by fit-for-purpose translational models."

Journal • Review • Oncology

Bioactivity studies of organometallic Cp*Rh(iii) and Au(i) NHC complexes bioconjugated to integrin binding peptides. (PubMed, RSC Med Chem) - "Tight-binding density functional theory (DFT) calculations at the αvβ3 Cilengitide pocket indicated that the Rh-RGD complex maintained the peptide recognition mode and dissociation energetics essentially unchanged, whereas Au-RGD engaged weakly with the binding pocket...However, inductively coupled plasma mass spectrometry (ICP-MS) revealed clear differences in metal uptake, with monomeric Au-RGD efficiently internalized, Rh-RGD closely matching its metal precursor, and Au-RGD 2 showing negligible accumulation. Altogether, these data pointed to a finely balanced interplay between integrin recognition, steric accessibility, solvation, and metal-centred reactivity, while emphasizing that successful c(RGD)-guided metallopeptides require optimization of organometallic chemistry, and vector design towards the development of the next-generation targeted metallodrugs."

Journal • Oncology

Irisin maintains ER homeostasis and activates AMPK via integrin αVβ5 to attenuate CSE + LPS-induced emphysema and inflammation. (PubMed, Respir Res) - "These findings suggest that through integrin αVβ5, irisin concurrently maintains ER homeostasis and activates AMPK, thereby alleviating CSE+LPS-induced emphysema and inflammation, suggesting a novel therapeutic direction for the management of AECOPD."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • ATF4 • HSPA5

Exercise-induced myokine irisin protects against obesity-associated ischemic stroke via integrin αVβ5 signaling. (PubMed, Front Pharmacol) - "Pharmacological blockade of integrin αVβ5 with cilengitide abolished the neuroprotective effects of irisin, establishing the receptor-dependent nature of its actions. These findings demonstrate that the FNDC5/irisin/integrin αVβ5 axis functions as a receptor-dependent, exercise-inducible neuroprotective pathway in obesity-associated ischemic stroke, and identify recombinant irisin as a promising ""exercise mimetic"" with therapeutic potential for this high-risk population."

Journal • Cardiovascular • Genetic Disorders • Inflammation • Ischemic stroke • Obesity • CLDN5 • NLRP3 • OCLN

Integrin-Associated Signalling Regulates Jagged1-Induced Osteogenic Differentiation of Human Dental Pulp Stem Cells. (PubMed, Int Dent J) - "Jagged1-induced osteogenic differentiation of hDPSCs requires integrin-dependent adhesion signalling but is not exclusively dependent on ITGB3 transcription. These findings support integrin-Notch crosstalk as a regulatory mechanism in hDPSC osteogenesis and provide a rationale for designing regenerative dental biomaterials that combine Notch-activating and adhesion-supportive cues."

Journal • HES1 • HEY1 • ITGB3 • RUNX2

Integrin inhibition differentially remodels vascular networks in lung metastases driven by vessel co-option or angiogenesis. (PubMed, Angiogenesis) - "Conversely, in angiogenic metastases, the vascular network induced by low-dose cilengitide fails to support immunocompetent microenvironmental features and is associated with increased chemotherapy resistance. This study provides the first evidence that co-opted vasculature can be therapeutically targeted via integrin inhibition, suggesting vascular normalization remodeling as a potential strategy to overcome resistance in tumors undergoing vessel co-option."

Journal • Oncology

Periostin drives psoriasis progression through the stimulation of cutaneous nerve fibers. (PubMed, iScience) - "Furthermore, applying cilengitide gel improved psoriatic skin lesions. Ultimately, this study identifies POSTN as a crucial regulator of cutaneous nerve fiber growth during psoriasis progression, highlighting its promise as a therapeutic target."

Journal • Dermatology • Immunology • Psoriasis • POSTN

Vitronectin-driven amyloid deposition disrupts mitochondrial homeostasis via integrin-mediated pathway in a humanized mouse model of transthyretin cardiac amyloidosis. (PubMed, Eur Heart J) - "Two reproducible ATTR-CM models that recapitulate the steadily progressive course of human disease were established. Furthermore, VTN actively drives cardiac amyloid deposition, and disruption of integrin αvβ3/FAK/Akt signalling links amyloid-ECM interactions to mitochondrial dysfunction. Therefore, modulation of integrin signalling represents a potential complementary therapeutic strategy in ATTR-CM beyond TTR suppression."

Journal • Preclinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • VTN

MiR-145-5p modulates collagen production and fibroblast behaviour after cardiac injury partially via COL5A1. (PubMed, Basic Res Cardiol) - "Furthermore, inhibition of miR-145-5p potentiated the suppression of TGF-β/SMAD signalling and the enhancement of fibroblast proliferation mediated by inhibiting integrin αvβ3 and αvβ5 with cilengitide. Collectively, miR-145-5p modulates collagen production and fibroblast behaviour partially via targeting COL5A1 and through integrin-mediated pathways."

Journal • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology • Inflammation • COL5A1 • MIR145 • TGFB1

In situ engineering of a self-healing drug-scaffold hydrogel to block platelet-driven postoperative metastasis. (PubMed, Biomaterials) - "Herein, we develop an injectable self-healing hydrogel (CS@Art-2CHO/Cil gel) co-delivering artesunate (Art) and integrin inhibitor Cilengitide (Cil) for local application...This dual "local clearance-systemic blockade" strategy synergistically prevents metastasis. This work presents a novel hydrogel paradigm that integrates precise mechanical adaptation with therapeutic synergy, offering a promising strategy against surgery-driven metastatic relapse."

Journal • Oncology

POSTN+ CAFs facilitate gastric cancer peritoneal metastasis by promoting ICAM-1-dependent tumor cell adhesion and CD8+ T-cell exhaustion. (PubMed, Front Immunol) - "Inhibiting POSTN downstream signaling with the integrin receptor antagonist Cilengitide, especially together with immune checkpoint blockade (anti-PD-1 and anti-CTLA-4), markedly reduced T-cell exhaustion and suppressed GCPM...POSTN may facilitates CAFs-tumor and CAFs-T-cell interactions through ICAM-1, thereby promoting metastasis and promoting immune evasion. Targeting the POSTN-ICAM-1 axis may provide a therapeutic approach to enhance immunotherapy efficacy and enhance immunotherapy outcomes in patients with GCPM."

IO biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • CAFs • CD8 • ETV3 • ICAM1 • POSTN

Macrophage-derived CTSZ promotes prostate cancer progression via αVβ3 integrin-mediated activation of the AKT/FOXO1/JUNB signaling axis. (PubMed, Cancer Cell Int) - "Our study identifies a novel pathway in which macrophage-derived CTSZ promotes PCa progression by driving M2 macrophage polarization and directly activating the αVβ3/AKT/FOXO1 axis in tumor cells, ultimately leading to JUNB downregulation. Targeting the CTSZ/αVβ3 axis may represent a promising therapeutic strategy for PCa treatment."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD163 • CD86 • JUNB

2-Hydroxyisobutyrylation and Phosphorylation Crosstalk Guides Metastasis Prediction and Immunotherapy in Esophageal Squamous Cell Carcinoma. (PubMed, MedComm (2020)) - "While combined treatment of integrin inhibitor cilengitide and immunotherapy exhibited targeted efficacy. By deciphering the mechanistic basis of Khib-phosphorylation crosstalk, identifying a novel plasma biomarker for lymph node metastasis, and providing a therapeutic strategy to sensitize tumors to immunotherapy, this work collectively advances the precision diagnosis and treatment of ESCC."

IO biomarker • Journal • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Interaction between CD82 and integrin αVβ3 selectively regulates collective movement of tumor cells via endolysosomal trafficking. (PubMed, Cell Mol Life Sci) - "Cilengitide, at the concentration that specifically inhibits integrin αVβ3, also selectively blocks collective movement, underscoring a promotive role of integrin αVβ3 in this mode of cell motility...Thus, our study reveals that i) integrin αVβ3 promotes collective movement of tumor cells, ii) CD82 counteracts this by diminishing integrin αVβ3 and its presence in microextrusions, and iii) digitation junction likely participates in collective cell movement. Our study further demonstrates that endolysosomal trafficking of CD82 and integrin αVβ3 is needed for their collective movement-regulatory activities and that coupling of metastasis suppressor CD82/KAI1 with different partners regulates different modes of cell movement."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Osteoclast-derived Del1 promotes pathological bone formation of AS via regulating RUNX2 expression in osteoblast (EULAR 2026) - "Additionally, DEL1 levels were measured in osteoclast-derived medium and human osteoblast precursor cells were treated with recombinant DEL1 protein and cilengitide trifluoroacetate, an integrin inhibitor for αvβ3...Conclusions Our findings establish DEL1 as a key osteoclast-derived coupling factor that drives pathological new bone formation in AS. By signaling through the Integrin αVβ3-RUNX2 axis, DEL1 promotes pathological bone formation and osteoblast differentiation, suggesting that targeting this pathway may offer a novel therapeutic strategy to prevent structural damage in AS patients."

Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Seronegative Spondyloarthropathies • EDIL3 • RUNX2

A vitronectin-functionalized ECM-mimetic hydrogel platform for modelling integrin-dependent tumour responses to cilengitide. (PubMed, Mater Today Bio) - "Together, these workflows provide a reproducible and scalable framework to investigate ECM-mediated regulation of neuroblastoma cell behaviour and drug response, with scope for quantitative image analysis of integrin-associated signals and ECM deposition. This ECM-mimetic hydrogel system offers a versatile and histology-compatible experimental platform for studying integrin-dependent tumour-matrix interactions and developing physiologically relevant in vitro-in vivo translational pipelines."

Journal • Neuroblastoma • Oncology • Solid Tumor • VCL • VTN

Osteoclast-derived DEL1 promotes pathological bone formation in ankylosing spondylitis by regulating RUNX2 expression in osteoblasts. (PubMed, Differentiation) - "Our findings establish DEL1 as a key osteoclast-derived coupling factor that drives new bone formation in AS. DEL1 promotes pathological bone formation and osteoblast differentiation by signaling through the integrin αVβ3-RUNX2 axis; targeting this pathway may offer a novel approach to prevent structural damage in patients with AS."

Journal • Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • EDIL3 • RUNX2

Integrin-targeting cyclic peptides suppress TGF-β1-driven EMT and invasion in third-generation EGFR-TKI-resistant NSCLC. (PubMed, Chem Biol Interact) - "Resistance to third-generation EGFR-TKIs such as naquotinib and osimertinib remains a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Among the derivatives, cilengitide (R-8) most effectively suppressed vimentin expression and ERK1/2 phosphorylation. Combination treatment with dovitinib further enhanced the inhibition of migration and invasion, suggesting synergistic potential."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TGFB1 • VIM

Integrin αvβ3-driven secretome remodeling uncovers THBS1 as a potential prognostic mediator in cutaneous T-cell lymphoma (AACR 2026) - "Here, we analyzed how integrin αvβ3 activation modulates the CTCL secretome using Mycosis Fungoides (MJ) and Sézary Syndrome (HuT78) cell lines treated with THs (T4=100 nM, T3=1 nM) with or without the αvβ3 inhibitor cilengitide (1.5 μM)...Together, our results show that physiological activation of integrin αvβ3 by THs reshapes the CTCL secretome toward a pro-tumorigenic and immunosuppressive state. THBS1 emerges as a potential prognostic mediator within this network, underscoring how systemic factors like hormones can influence lymphoma progression and revealing new molecular targets with diagnostic and therapeutic relevance."

Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • ITGB3 • KDR • TGFB1 • THBS1 • TLN1

Thyroid hormones as systemic regulators of melanoma progression and dissemination (AACR 2026) - "Functional assays demonstrated that physiological and supraphysiological TH concentrations increased ME cell proliferation by 20-40% (p<0.01), an effect prevented by the αVβ3 inhibitor cilengitide (p<0.05), indicating that THs promote melanoma growth predominantly through αVβ3-mediated signaling...However, tumor-draining lymph nodes from hyperthyroid mice showed reduced cytotoxic CD8⁺ T lymphocytes (p<0.05), while spleens from hypothyroid mice exhibited increased B lymphocytes (p<0.01) and myeloid-derived suppressor cells (p<0.05), suggesting that TH status modulates systemic immune cell distribution.Overall, these findings demonstrate that thyroid hormones exert dual and context-dependent effects on melanoma: TH excess enhances primary tumor growth through integrin αVβ3 signaling, whereas TH deficiency promotes metastatic dissemination, likely through modulation of systemic antitumor immunity. The thyroid axis emerges as a novel systemic regulator and..."

IO biomarker • Melanoma • Oncology • Skin Cancer • Solid Tumor • CD8

Integrin αVβ3 activation by thyroid hormones triggers JAK/STAT oncogenic pathways that promote T cell lymphoma dissemination (AACR 2024) - "Although the FDA approved the use of inhibitors to target this pathway (Ruxolitinib), significant toxic effects have been reported and their use is limited...We found that THs induced STAT1, 3 and 5 phosphorylation in TCL cells and that the integrin αVβ3 inhibitor, Cilengitide (Cile) blunted these effects (p<0.05)...Finally, we evaluated the dissemination of TCL in an in vivo model (by vain tail) and found that BexT4+Cile reduced EL4 cell implantation into the liver and kidneys (p<0.05). These results described the mechanisms by which THs induce the activation of JAK/STAT oncogenic pathway and showed how the inhibition of integrin αvβ3 in combination with bexarotene has therapeutic potential for TCL."

Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • MMP2 • MMP9 • STAT1

Cancer-associated fibroblasts-derived periostin promotes lymph node metastasis of cholangiocarcinoma through lymphatic endothelial reprogramming (AACR 2025) - "This study uncovers the novel role of CAF-derived POSTN in promoting LNM of CCA, presenting the potential therapeutic promise of the FDA-approved αVβ3/5 inhibitor, Cilengitide, in inhibiting LNM in CCA."

Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CTCs • ITGB3 • POSTN

Engineered hydrogel platform reveals integrin-ECM mechanisms and therapeutic targets in esophageal adenocarcinoma (AACR 2025) - "This study establishes an engineered biomaterial platform that recapitulates key ECM biochemical properties, providing a foundation for pre-clinical drug testing and mechanistic studies. Our data indicate that αvβ3 integrin-mediated adhesion is critical for EAC PDO growth and activation of oncogenic pathways. The efficacy of cilengitide within this model suggests that targeting fibronectin-integrin αvβ3 interactions could be a viable therapeutic strategy for EAC when combined with chemotherapy."

Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Solid Tumor

Cartilage oligomeric matrix protein as a potential biomarker and therapeutic target of radiation resistance in NSCLC (AACR 2024) - "Plated cells in monolayer were treated with either COMP (2µg/mL) or PBS (control), and then within each group received either: 1] one of two different inhibitors of COMP signaling (either the αᵥ integrin antagonist cilengitide (1µM), or the Src inhibitor PP2 (1µM)), or 2] no additional treatment...In conclusion, COMP serves to radioprotect NSCLC in an undetermined manner, and could serve as both a prognostic biomarker for and therapeutic target against radiation resistance in patients with NSCLC. Support: Milton Raben Foundation"

Biomarker • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • COMP

Cilengitide sensitivity is predicted by overall integrin expression in breast cancer (AACR 2025) - "We tested an additional pan-ITGAV inhibitor (GLPG0187) to determine how generalizable our findings on cilengitide sensitivity might be to integrin inhibition. Integrin inhibitors are appealing candidates to pursue as anti-cancer drugs because they are generally well-tolerated, but their efficacy is mixed, possibly due to the absence of predictive markers. Cilengitide induces death in breast cancer cells with low integrin abundance, where complementary ECM promotes survival. Thus, integrin inhibition in breast cancer warrants further study."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • FN1 • ITGA3 • ITGA6 • ITGB3 • ITGB4 • ITGB5