Cilcane (cilengitide)

Consistently, combination of the ALK TKI alectinib with the MET TKI capmatinib and/or the integrin inhibitor cilengitide was significantly more efficacious than single agent treatment in suppressing tumor growth using an in vivo EML4-ALK -dependent allograft mouse model of NSCLC. In summary, these findings emphasize the complexity of resistance-associated crosstalk between CAFs and cancer cells, which can involve multiple concurrent signaling pathways, and illustrate how comprehensive elucidation of paracrine and juxtacrine resistance mechanisms can inform on more effective therapeutic approaches.

The combination of trastuzumab and cilengitide showed a synergistic effect, reducing both EMT and Hedgehog pathway activity. Targeting ITGβ3 with cilengitide, combined with trastuzumab, effectively suppresses the Hedgehog pathway and EMT, offering a potential strategy to overcome trastuzumab resistance and improve outcomes for HER2-positive breast cancer patients.

To confirm the functional involvement of ectosomal integrins in functional tests (Alamar Blue, wound healing and tube formation assays), ectosomes were also pretreated with anti-integrin antibodies and integrin-blocking peptides echistatin and cilengitide...The study demonstrated the functional role of ectosomal αvβ3 and αvβ5 integrins. It also provided a baseline understanding of ectosome-mediated αvβ3 integrin/TNF-α and αvβ5 integrin/VEGF signaling in angiogenesis.

In this study, the role of integrins and TGF-β signalling in vemurafenib resistance in melanoma was investigated, and the potential of combining vemurafenib with cilengitide as a therapeutic strategy was investigated. Additionally, this combination therapy significantly decreased invasion and colony formation in these resistant cells. In conclusion, it is suggested that targeting integrins and TGF-β signalling, specifically ITGA5, ITGB3, PAI1, and p21, may offer promising approaches to overcoming vemurafenib resistance, thereby improving outcomes for metastatic melanoma patients.

The combination of trastuzumab and cilengitide, an integrin inhibitor, significantly decreases the expression of stem cell markers in resistant cells, indicating a potential therapeutic strategy to overcome resistance. These results identify the importance of ITGβ3 in mediating stemness and trastuzumab resistance through Notch signalling in HER2-positive breast cancer, offering new approaches for enhancing treatment efficacy.

Activated TGFβ1 has a superior capacity in predicting radiation pneumonitis (RP) risk and plays a vital role in the development of radiation-induced pulmonary fibrosis (RIPF). Conditional knock out Itgav in myofibroblasts prevented mice from developing RIPF. Cilengitide alleviated the development of RIPF by inhibiting αv integrin-mediated TGFβ1 activation and may be used in targeted approaches for preventing RIPF.

With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.

Topical applications of αvβ3 antagonists yield therapeutic benefits in EDE by promoting corneal epithelial defect healing and reducing inflammation. Antagonistic targeting αvβ3 may be a novel promising strategy to treat patients with dry eye disease.

In A549GR cells, cRGDwV and cRGDyV showed inhibitory effects on the expression of mesenchymal marker expression, migration, and invasion. These results indicate that cyclic RGD peptides containing aromatic amino acids can be used to inhibit mesenchymal marker expression as well as migration and invasion in gefitinib-resistant cells.

In addition, the present study revealed the efficacy of cilengitide for reducing αvβ3 expression, with a mean αvβ3 positivity of 34.17% in cilengitide treated material vs 66.14% in control and with less tumor growth when combined with etoposide, with a final mean volume of 0.04 cm in combined therapy vs 1.45 cm in control. The results of this work highlight the importance of extracellular matrix-focused therapies in preclinical studies to improve therapeutic assessment for high-risk neuroblastoma patients.

To sum up, we revealed previously unrecognized action mechanisms of CD51 on HCC progression and uncovered the underlying cause of cilengitide treatment failure and supported the translational prospects of combined CD51-targeted therapy in the clinic.

This is the oldest reported GBM patient with greater than 10-year survival. Her exceptional response may have been influenced by MGMT promoter methylation status and PTEN expression.

In vivo experiments showed that LV-ETS1 Exos promoted omental metastasis of ovarian cancer by mediating the tumor-promoting effect of macrophages, which could be neutralized by integrin ανβ5 inhibitor cilengitide. These results indicated that ETS1 could drive ovarian cancer cells to release exosomes with higher laminin levels, thereby accelerating the exosome-mediated pro-metastatic effects of omental macrophages via the integrin αvβ5/AKT/Sp1 signaling pathway, and the integrin ανβ5 inhibitor cilengitide could inhibit omental metastasis of ovarian cancer driven by tumor-derived exosomes.

Compared with erlotinib alone, combination treatment with cilengitide led to an enhanced inhibitory effect on TGF-β1-induced expression of mesenchymal markers and invasion in non-small cell lung cancer A549 cells. These results suggest that cilengitide could improve anticancer drug efficacy and contribute to improved treatment strategies to inhibit and prevent EMT-based cancer progression.

Blockade of EDIL3-integrin αβ interaction by cilengitide restores sensitivity to paclitaxel and reverts EMT in paclitaxel-resistant cancer cells. Combinations of cilengitide and taxanes could be beneficial in the treatment of subsets of breast and prostate cancers.

The POSTN/TGFβ1 positive feedback pathway regulates the expression of stemness factors and the malignant progression of HCC cells by regulating the transcriptional activation of AP-2α. This pathway may serve as a new target for targeted gene therapy in HCC.

We suggested that the use of cilengitide can improve the efficacy of anti-cancer drugs in combination drug-based chemotherapy. These results provide an improved therapeutic strategy for treating and preventing EMT-related disorders, such as NSCLC, lung fibrosis, cancer metastasis, and relapse.

Then, patient-derived GBM cells grown in monolayers on precoated laminin, vitronectin, or fibronectin substrates were treated with cilengitide, an integrin inhibitor, and/or carmustine, an alkylating chemotherapy. EGFR expression increased with integrin α knockdown GBM cells and may represent a compensatory survival mechanism. These results indicate that ECM proteins confer CAMDR through integrin α in GBM cells.

Blockade of EDIL3-integrin αβ interaction by cilengitide restores sensitivity to paclitaxel and reverts EMT in paclitaxel-resistant cancer cells. Combinations of cilengitide and taxanes could be beneficial in the treatment of subsets of breast and prostate cancers.

Also, integrin αvβ3 positive NSCLC cells revealed significant EGFR inhibitors resistance, resulting from the activation of Galectin-3/KRAS/RalB/TBK1/NF-κB signaling pathway. Co-encapsulating integrin αvβ3 inhibitor and EGFR inhibitor further improved the drug delivery system, leading to superior anti-cancer effects and reduced systemic toxicity.  Our results demonstrated thatco-encapsulation of erlotinib and cilengitide by MPEG-PLA (Erlo+Cilen/PP) nanoparticles revealed enhanced tumor suppression along with reduced organ damages, providing an innovative approach for NSCLC treatment.

For PFS, erlotinib (Erlo)+bevacizumab (Bev) (HR 0.26, 95% CrI: 0.08-0.75 vs placebo), osimertinib (Osi) (HR 0.29, 0.11-0.70 vs placebo), and afatinib (Afa) were top-ranking individual treatments, while immunotherapy (IT)+anti-VEGFR (aVEGFR)+platinum-based therapy (Plat) (HR 0.42, 0.06-2.63 vs placebo), EGFR-TKI (ET)+aVEGFR (HR 0.35, 0.14-0.85 vs placebo), and ET+aVEGFR+Plat were top-ranking medication classes. For OS, Osi (HR 0.52, 0.10-2.00 vs placebo), cetuximab (Cet)+Bev+Plat (HR 0.51, 0.06-3.38 vs placebo), and cilengitide (Cil)+Cet+Plat were top-ranking individual treatments, while ET+aVEGFR+Plat, ET+Plat, and third-generation EGFR-TKI (3 ET) were top-ranking medication classes. For PFS regarding the EGFR genomic aberration status, Erlo+Bev, Osi, and Afa were superior for exon 19 deletion status, whereas ET+Bev, Osi, and gefitinib (Gef)+pemetrexed (Peme) were excellent for exon 21 L858Arg mutation status...Osi, Erlo+Bev, and Erlo+Bev+Plat are reasonably recommended to balance PFS and OS, but adverse events should be considered. IT+aVEGFR+Plat shows potential superiority, but more clinical evidence is needed.

The effectiveness of an ITGAV antagonist, cilengitide, for breast cancer treatment was investigated in vivo...Targeting ITGAV is a potential treatment for metastatic breast cancer as well as primary breast tumors with high ITGAV expression. ITGAV expression levels may be useful predictors of patient treatment and outcome responses.