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.

ITGA3 acts as an oncogenic driver in GC by facilitating glutamine uptake via the STAT3-SLC1A5 signaling axis. These findings suggest that therapeutic targeting of this pathway could represent a promising approach for the clinical management of GC.

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.

Functional assays demonstrated that CD51 enhances CSC properties, including tumorsphere formation, migration, invasion, and oxaliplatin resistance. Pharmacological inhibition of CD51 using cilengitide suppressed CSC phenotypes in vitro and inhibited tumor growth in patient-derived organoids and xenograft models. These findings establish CD51 as a novel CSC biomarker and therapeutic target, offering a strategy to disrupt Notch-dependent stemness and chemoresistance in GC.

Furthermore, we observed that the integrin αvβ3 inhibitor, cilengitide, not only reverts these effects but also enhances the anti-lymphoma activity to a greater extent than the JAK1/2 inhibitor, ruxolitinib, when combined with bexarotene, a synthetic rexinoid clinically used for cutaneous TCL treatment. Additionally, we observed that high integrin αvβ3 mRNA levels are enriched in pathways associated with lymphoma progression and reduce overall survival in TCL patient samples. Our findings support the therapeutic potential of targeting THs signaling through integrin αvβ3 inhibition in combination with bexarotene as a less toxic therapeutic strategy to mitigate aberrant JAK/STAT activation and limit lymphoma dissemination.

Importantly, pharmacological disruption of FN1-integrin α5β1 signaling using Cilengitide effectively reprogrammed the tumor immune landscape and suppressed tumor growth in mice models. These findings establish FAP+ CAF-derived FN1 as a critical orchestrator of tumor immunosuppression and identify the FN1-integrin α5β1 axis as a promising therapeutic target in breast cancer.

Inhibition of integrin αVβ3 by antagonist cilengitide (CGT) and shRNA significantly reduce the cell viability of ovarian cancer cells. Co-treatment of CGT and cisplatin induced synergistic cytotoxicity in SKOV3 cells...The cell migration ability of SKOV3 cells was blunted by CGT by tumor spheroid-based migration assay. This study used 2D and 3D cell models to provide novel insight into ovarian cancer therapy by targeting integrin αVβ3 and suitable cell models for searching integrin αVβ3-targeting drugs.

Targeting ITGβ3, alone or in combination with cilengitide, offers a promising strategy to resensitize resistant HER2-positive breast cancer cells to Trastuzumab. These findings provide valuable insights into the mechanisms of Trastuzumab resistance and suggest potential therapeutic avenues for improving patient outcomes.

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.