Cilcane (cilengitide)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

These findings identify integrin αV as a promising molecular target for TAA intervention. However, they also highlight concerns regarding the clinical use of integrin αV inhibitors, which are currently under investigation in cancer trials, as they may increase the risk of TAA or AD development.

Additionally, Cilengitide significantly improves anti-PD-1 immunotherapy efficacy, offering a potential therapeutic strategy to counteract PNI-driven immunosuppression. This study identifies ITGA5 as a key promoter of tumor invasion into nerves, enhancing NGF release from Schwann cells and altering the immune landscape to favor tumor growth. These findings open new avenues for therapies targeting these interactions in cancer progression.