Cilcane (cilengitide) / Iceni Pharma - LARVOL DELTA

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

DANEELpath open source digital analysis tools for histopathological research in neuroblastoma models. (PubMed, Sci Rep) - "Three-dimensional (3D) hydrogels are an emerging biomimetic tool with significant potential for studying the role of ECM elements and testing new mechano-drugs such as cilengitide, a potential therapeutic agent to treat high-risk NB due to its ability to inhibit VN activity in cells...DANEELpath integrates deep learning techniques, specific segmentation of individual and cluster cells through mathematical morphology pipelines, and extraction of spatial features within whole-slide images. Thanks to its versatility, DANEELpath is adaptable to address different biological questions and has significant potential for use in a variety of research fields and model systems, which could help advance biomedical discovery."

Journal • Neuroblastoma • Oncology • Solid Tumor • VTN

Integrin-Mediated TIMP1 Signaling Reprograms Liver Macrophages and Accelerates Colorectal Cancer Metastasis. (PubMed, Cells) - "CRC-derived TIMP1 remodels liver macrophages via the CD63/β1-integrin-AKT/mTOR pathway to promote a hepatic pre-metastatic niche. Pharmacologic inhibition of this signaling axis with the integrin antagonist cilengitide suppressed macrophage M2 markers and liver colonization in mice, supporting TIMP1-integrin signaling as a potential therapeutic target."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CD63 • CSF1 • IRF4 • TIMP1

Integrin inhibition facilitates fibrocartilaginous transformation in connective tissue in osteoarthritis. (PubMed, Sci Adv) - "In OA mouse models and a TMJ-OA miniature pig model, inhibition of integrin αV/β5 activity using cilengitide facilitated the transcriptional reprogramming of Col5a1+ fibroblast and functional remodeling of the connective tissues. Our findings verified the effectiveness of cilengitide and provided a clinical route for fibrocartilage injury repair in OA."

Journal • Immunology • Musculoskeletal Diseases • Osteoarthritis • Pain • Rheumatology • COL5A1

Combined treatment of TKIs with Cilengitide overcomes afatinib-resistance in EGFR-mutated NSCLC cells. (PubMed, Mol Biol Rep) - "Our findings demonstrate that cilengitide, a cyclic RGD peptide, effectively suppresses invasion and migration in afatinib-resistant NSCLC cells through inhibition of the integrin-FAK signaling axis. Although cilengitide showed limited growth inhibition as a monotherapy, its combination with TKIs such as afatinib or dovitinib significantly enhanced anti-proliferative and anti-invasive effects. These synergistic outcomes were associated with reduced expression of integrin-mediated proteins and MMPs, suggesting that cilengitide may potentiate TKI efficacy by modulating the tumor microenvironment and migratory potential of resistant cells. Taken together, this study supports the potential of cilengitide as an adjuvant therapeutic strategy in treating EGFR-TKI-resistant NSCLC. Further validation through preclinical animal models and pharmacokinetic studies will be crucial for future clinical translation."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDH2 • EGFR • TGFB1 • VIM • VTN

Cancer-associated fibroblasts confer ALK inhibitor resistance in EML4-ALK-driven lung cancer by concurrent integrin and MET signaling. (PubMed, Sci Signal) - "Moreover, the combination of the ALK inhibitor alectinib with the MET inhibitor capmatinib and/or the integrin inhibitor cilengitide was more effective than single-agent treatment in suppressing tumor growth in allografted mice. The findings illustrate a previously unappreciated complex nature of concurrent paracrine and juxtacrine mechanisms of CAF-driven resistance that may inform the development of more effective therapeutic approaches."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAFs • EML4

Lost in translation: Do preclinical studies predict clinical failure in GBM? (SNO 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (SNO 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (WFNOS 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Oncology • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (WFNOS 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Glioma • Oncology • Solid Tumor

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (SNO 2025) - "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (SNO 2025) - "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

RUNX2, IBSP, and SPP1 as Key Molecular Nodes in Calcific Aortic Stenosis: Transcriptomic Diagnostics and Emerging Therapeutic Targets. (AHA 2025) - "MEK inhibitors (trametinib, selumetinib) downregulate RUNX2 via MAPK/ERK pathway inhibition. Epigenetic modulators (vorinostat, valproic acid) could suppress RUNX2 transcriptionally. The integrin antagonist cilengitide blocks αvβ3, disrupting IBSP/SPP1-mediated signaling. While these agents are approved for oncology or neurology, their utility in valve calcification remains investigational.In summary, this study highlights RUNX2, IBSP, and SPP1 as transcriptomic biomarkers and actionable therapeutic targets in CAS. Their expression profiles, biological roles, and druggability make them high-priority candidates for future diagnostic tools and targeted interventions in a disease currently reliant on surgical replacement."

Cardiovascular • Immune Modulation • Immunology • RUNX2 • SPP1

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (WFNOS 2025) - "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (WFNOS 2025) - P2 | "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

Critical Role of the Endothelial αV/β5 Integrin Receptor Signaling Pathway in Promoting Irisin-induced Hippocampal BDNF Expression. (PubMed, Mol Neurobiol) - "Our findings indicated that recombinant irisin (r-irisin) treatment of hippocampal slices led to an increase in BDNF expression and that this effect was blocked by cilengitide, an αV/β5 integrin antagonist...Additionally, αV/β5 integrins, phosphorylated endothelial NO synthase (p-eNOS), and BDNF were significantly elevated in the hippocampal endothelial cells of exercised rats. These findings reveal that irisin may upregulate BDNF expression in the hippocampal through a mechanism dependent on endothelial αV/β5 integrins and the FAK/eNOS signaling pathway, supporting its potential as a therapeutic target for enhancing NO-dependent BDNF expression."

Journal • NOS3

Proteomic Analysis of Thyroid Hormone-Induced Secretome in Cutaneous T Cell Lymphoma (ASH 2024) - "This study aims to determine and contrast the proteins secreted (i) under basal conditions and (ii) in the presence of THs with or without the integrin αVβ3 pharmacological inhibitor, cilengitide (cile)...In summary, our study has shed light on the crucial role of THs as regulators of HuT78 and MJ secretome. These findings are of significant importance, as they provide a solid basis for further investigation into the role of these soluble factors and their receptors in the CTCL microenvironment."

IO biomarker • Omic analysis • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • BCL2L1 • CDK1 • HIF1A • IL2 • ITGB3 • MAPK14 • PD-1 • PD-L1 • PSMA1 • SLC2A1 • TGFB1 • THY1 • TLN1 • UCHL5 • VAV1 • ZAP70

Spatial-reprogramming derived GPNMB+ macrophages interact with COL6A3+ fibroblasts to enhance vascular fibrosis in glioblastoma. (PubMed, Genome Med) - "Our findings highlight the critical role of COL6A3+ TAFs in regulating MDM function and spatial distribution, as well as their contribution to fibrotic tumor vasculature formation. Additionally, we propose targeting COL6A3+ TAFs with cilengitide as a potential therapeutic strategy."

Journal • Brain Cancer • Fibrosis • Glioblastoma • Immunology • Oncology • Solid Tumor • COL6A3 • GPNMB • ITGB5

Chemoselective sulfonyl fluoride exchange (SuFEx)-induced macrocyclization of tyrosine-containing peptides in aqueous media. (PubMed, Chem Sci) - "To demonstrate the scope and translational potential of the method, STEMtide analogs of several clinically relevant peptides, including leuprorelin, β-MSH, liraglutide, and cilengitide, a cyclic RGD peptidomimetic, were successfully synthesized in high yield using the SuFEx-mediated strategy. RGD STEMtide analogs exhibited low toxicity to MCF-7 cells, as well as potent inhibition of cell adhesion comparable to cilengitide itself, highlighting the therapeutic potential of this new class of peptide macrocycles."

Journal

Transcriptome-Based Identification of Biomarkers Associated With Sphingosine-1-Phosphate Signaling Pathway in Aortic Dissection. (PubMed, Int J Hypertens) - "Finally, seven potential small-molecule drugs targeting ITGA5 were predicted, including cilmostim, cilengitide, and dimethyl sulfoxide. This study identifies ITGA5 as a novel biomarker for S1P-associated AD and reveals its potential underlying mechanisms and therapeutic candidates, providing a theoretical foundation for AD diagnosis and treatment."

Biomarker • Journal • CD4 • CXCL5 • ITGA5

The Integrin Inhibitor Cilengitide Targets CCN1-Mediated Angiogenesis and Reduces Disease Severity in a Preclinical Rheumatoid Arthritis Model (ACR Convergence 2025) - "Cilengitide effectively inhibits CCN1-induced angiogenesis in vitro, confirming that CCN1 exerts its effects on endothelial cells through integrins αvβ3 and αvβ5. In vivo, Cilengitide significantly reduces clinical, structural, and histological damage in the Tg197 arthritis model while modulating immune profiles. These findings suggest that CCN1's effects in RA, including structural and inflammatory damage, are mediated by its role in promoting pathological angiogenesis."

IO biomarker • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CCN1 • CD4 • PD-1

B3GNT2 Regulates Integrin β3 Glycosylation and Th17/Treg Imbalance in Axial Spondyloarthritis Pathogenesis (ACR Convergence 2025) - "This study demonstrates that rs6759298 reduces B3GNT2 gene expression, thereby altering the glycosylation of ITGB3 and promoting the progression of AS. These findings offer new insights into the immune mechanisms underlying AS."

Ankylosing Spondylitis • Immunology • Inflammation • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • ITGB3

TGFβ enhances platelet-breast-cancer-cell interaction and promotes platelet aggregation. (PubMed, FEBS J) - "Furthermore, we selected specific inhibitors of integrin-αv (cilengitide) and galectin-3 (GB1107) that did not interfere with PLT aggregation itself...Complementary analyses of proteomic datasets from breast cancer tissues demonstrated a significant positive correlation between TGFβ1 and the platelet marker integrin alpha-IIb (ITGA2B; also known as CD41), particularly in luminal A subtypes and in cancers with lymph node involvement. These findings suggest that TGFβ stimulation enhances PLT-breast-cancer cell interactions and promotes PLT aggregation through the upregulation of specific adhesion proteins, thereby potentially contributing to CAT and metastatic progression."

Journal • Breast Cancer • Cardiovascular • Hematological Disorders • Oncology • Solid Tumor • Thrombosis • ITGA2B • TGFB1

KIF1Bβ suppresses hepatocellular carcinoma by transporting and secreting FBLN5 to attenuate the integrin pathway. (PubMed, Gut) - "Our findings shed light on the genetic and molecular mechanisms of the HCC-associated susceptibility locus at 1p36.22 and provide potential new strategies for the treatment of HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • KIF1B