Endostar (recombinant human endostatin)

Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

P2, N=16, Recruiting, Nanjing First Hospital, Nanjing Medical University

In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.

P2, N=126, Completed, Xinqiao Hospital of Chongqing | Unknown status --> Completed

Endostar combined with cisplatin might exert anti-tumor effects by down-regulating the expression of METTL3 and FMOD.

The ongoing ENPOWER study exploring the efficacy and safety of the recombinant human endostatin (endostar) combined with programmed cell death 1 antibody sintilimab and chemotherapy showed encouraging efficacy and safety in advanced non-squamous non-small cell lung cancer. No antiangiogenesis-related adverse events were observed. The current study showed that EIC was potentially effective for patients with NSCLCnm, especially when used as first-line therapy, and well tolerated.

This prospective study showed that Envafolimab combined with Endostar has promising efficacy and good tolerability in advanced NSCLC with PD-L11%. This combination provided a new choice and a prospective study in furture was expected.

Our findings suggest that no statistical significance between above vascular targeting regimens. Pathological type of lung cancer may affect the effect of bevacizumab intracavity infusion plus chemotherapy. The influence of different administration routes of vascular targeting drugs on efficacy remains to be investigated. There are some concerns with the quality of the studies, and some limitations should be considered when interpreting these results, which includes limited geographical region and sample size of studies. Despite these limitations, this study may inform vascular targeting therapy choice in such a patient population.

P2, N=40, Recruiting, The First People's Hospital of Lianyungang | Not yet recruiting --> Recruiting | Trial completion date: Jan 2024 --> Jun 2024 | Trial primary completion date: Jan 2023 --> May 2024

P2, N=43, Recruiting, Fudan University

Different angiogenic and immunosuppressive effects are observed between particle therapy and conventional X-ray radiotherapy. The combination of RE, particle therapy and immunotherapy presents a promising future therapeutic triad for NSCLC.

P=N/A, N=30, Not yet recruiting, Peking University Third Hospital

Interestingly, Rh-endostatin-induced cardiotoxicity was inhibited by dihydromyricetin (DHM) both in cultured cells in vitro and in mouse hearts in vivo. The study provides new inside into rh-endostatin-induced cardiotoxicity and identified a novel potential medication DHM to overcome the serious adverse effect.

For newly diagnosed BMs, adding chemotherapy, EGFR-TKIs, and other innovative systemic agents (temozolomide, nitroglycerin, endostar, enzastaurin, and veliparib) to radiotherapy did not significantly prolong OS than radiotherapy alone; whereas radiotherapy + nitroglycerin showed significantly better CNS-PFS and ORR...For previously treated BMs, pembrolizumab + chemotherapy, nivolumab + ipilimumab, and cemiplimab significantly prolonged OS than chemotherapy alone...The value of surgery should also be emphasized. The result should be further confirmed by RCTs.

These indicate that rES-CSP may play a role in inhibiting tumor growth and metastasis by down-regulating the angiogenic factor VEGF and the metastasis-related molecules or by interfering with HSPGs-mediated tumor metastasis.

As compared with the control group, EH/TCLN treatment led to significantly reduced tumor angiogenesis and expression of tumor microenvironment-related cytokines (TMCs), increased proportion of CD8 T cells in the spleen, lymph node and tumor, elevated activity of cytotoxic T lymphocytes (CTLs) and tumor cell apoptosis. The present study demonstrated that the EH/TCLN treatment effectively created a favorable immune microenvironment for the induction of antitumor immunity and improved antitumor immune responses.

P2, N=100, Recruiting, Qianfoshan Hospital

The trastuzumab biosimilar drug HLX02 exhibited good treatment efficacy in HER2-positive gastric cancer, especially when combined with Endostar. IVIM-DWI can noninvasively monitor the process of vascular normalization and reflect the treatment effect early at the molecular level.

Our findings provide experimental evidence and a theoretical basis for the application of Endostar in combination with irradiation for anti-cervical cancer treatment.

The combination of PD-1 and Endostar suppressed brain metastases of NSCLC.

Tumor angiogenesis inhibitors such as Bevacizumab, Ramucirumab and Endostar have been applied to the therapy of non-small cell lung carcinoma (NSCLC) patients, especially for lung adenocarcinoma (LUAD)...Moreover, apigenein showed perfect anti-angiogenic effect in xengraft model of LUSC cell NCI-H1703 cells, indicating it may be developed into a potential angiogenesis inhibitor for LUSC patient. Collectively, our study provides new insights into the anti-tumor mechanism of apigenin and suggests that apigenin is a safe and effective angiogenesis inhibitor for NSCLC therapy.

ALK fusion is a risk factor for brain metastasis (BM) in patients with advanced non-small NSCLC patients. In our case, a novel CLHC1/RNT4 intergenic region, ALK fusion, was identified for the first time in a lung adenocarcinoma patient with BM, who benefited from crizotinib and endostar sequential alectinib. Our case highlights the advantages of NGS for fusion detection and provides promising treatment options for NSCLC patients with BM harboring ALK fusions.

This study is first to assess nivolumab plus rh-endostatin in previously treated patients with advanced NSCLC. In view of its favorable efficacy and safety profile, this combination represents a promising treatment regimen in this patient population.

P2, N=40, Not yet recruiting, The First People's Hospital of Lianyungang

Weekly cisplatin was administered concurrently with IMRT...In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

P1, N=24, Not yet recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd.

Collectively, these results demonstrate that EnDuo exhibits a comparable anti-metastatic effect by suppressing the migration of colon cancer cells. Possibly, EnDuo interrupts the PI3K/AKT/ERK signaling pathway to arrest cell migration. Our study provides a novel insight to the potential clinical applications of EnDuo against colon cancers in the future.

An appropriate amount of anti-angiogenic agents can reconstruct tumor blood vessels in a short period of time and form vascular homeostasis, increase the function of blood vessel perfusion and reverse the multidrug resistance of chemotherapy, which is also called "vascular normalization." Endostar (a recombinant human endostatin) was developed by China and as a multi-target anti-angiogenesis agent...In this study, the patients with cervical cancer within stage IIB2 were selected, endostar combined with cisplatin+paclitaxel neoadjuvant chemotherapy (NACT) before radical surgical operation was adopted, patients outcome and adverse reaction were followed up...Endostar restored vascular homeostasis in cervical cancer temporarily, enhanced chemotherapeutic agents effects in cervical cancer, increased patient OS ratio. Endostar+NACT treatment may provide a new target therapy for cervical cancer.

CEUS-guided TACE treatment of HCC can effectively inhibit tumor angiogenesis, control tumor progression, and prolong the survival of patients, which is conducive to the prognosis of patients.

Furthermore, ES reduced the expression of PD-L1 and suppressed the phosphorylation of STAT3 in ovarian cancer cell lines. ES blocked the metastasis, invasion and angiogenesis of ovarian cancer cells by suppressing the activation of PD-L1 and STAT3, which might be considered as the potential mechanism of ES in the treatment of ovarian cancer.

CXCR4 expression, which is involved in TAM recruitment, increased following RT, whereas, ES attenuated its expression. Our findings suggest that ES can promote the normalization of tumor blood vessels and increase the anti-tumor immune-related immune cells infiltrating the tumor following RT treatment.

Endostar combined with radiotherapy can inhibit tumor growth and downregulate the expression levels of TGF-β1 and IL-10 through synergistic action.

P2, N=106, Not yet recruiting, First Affiliated Hospital of Guangxi Medical University

Furthermore, the number of apoptotic cells was highest in the CD/ES-EPC group. The EPCs transfected with CD/ES inhibited tumor growth and preferentially induced tumor cell apoptosis, providing a novel methodology for cancer-targeting therapy.

In summary, our study demonstrated that endostatin inhibited angiogenesis. The downregulation of the Wnt/β-catenin pathway may be engaged in the suppression of angiogenesis by endostatin in bladder cancer cells and cancer stem cells.

Platinum combined with paclitaxel or gemcitabine were administered with endostar in 55% of pts. Endostar combined with chemotherapy was effective and well tolerated for the treatment of HER-2 negative ABC, especially TNBC. Its efficacy and safety could be further studied in randomized trials. Research Funding: Simcere

The combination of anti-PD-1 and endostar has a remarkably synergic effect on LLC tumour growth by means of improving the tumour microenvironment and activating autophagy.

This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent in vitro...PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro. Overall, these results suggest that PEP06 polypeptide 30 inhibiting αv integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

Regardless of what kind of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) and chemotherapy regimens were used previously, all patients gained longer PFS in the anlotinib group, while only patients treated with vinorelbine/platinum in the EGFR wild type group, pemetrexed/platinum, vinorelbine/platinum, and gefitinib in the EGFR mutation group, and EGFR TKI used as the first line group could benefit from anlotinib on OS...This study indicated that previous bevacizumab or endostatin treatments had no impact on the efficiency of anlotinib. Patients with CRT history benefited more from anlotinib on PFS. EGFR TKI and chemotherapy treatment history had more impact on OS than PFS in patients treated with anlotinib compared to placebo.