P2, N=32, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Initiation date: Oct 2023 --> Feb 2024

This demonstrates the potential of leveraging deep learning for accurate VEGF prediction as a powerful tool to accelerate research, streamline drug discovery and uncover novel therapeutic targets. This insightful approach holds promise for expanding our knowledge of VEGF's role in health and disease.Communicated by Ramaswamy H. Sarma.

The combination of sapanisertib and ziv-aflibercept was generally tolerable and demonstrated anti-tumor activity in heavily pre-treated patients with advanced malignancies.

P1, N=83, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Jan 2024

P1, N=83, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025

P=N/A, N=140, Completed, Sanofi | Active, not recruiting --> Completed

Although limited by sample size and follow-up, these findings highlight the potential of the combination of ziv-aflibercept antiangiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment and the need for further research to improve outcomes in anti-PD-1-resistant melanoma.

P1, N=78, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=30, Recruiting, Panolos Bioscience

P2, N=114, Completed, CSL Behring | Phase classification: P2a --> P2

P2, N=32, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

P3, N=202, Active, not recruiting, GCS IHFB Cognacq-Jay | Recruiting --> Active, not recruiting | Trial completion date: Aug 2023 --> Jun 2024 | Trial primary completion date: Oct 2022 --> Jun 2023

P1, N=30, Recruiting, Panolos Bioscience | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, Panolos Bioscience

P2, N=19, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism. In conclusion, the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.

The apoptotic effects of C-VGB3 on HUVE and 4T1 MCT cells were inferred from annexin-PI and TUNEL staining and activation of P53, caspase-3, caspase-7, and PARP1, which mechanistically occurred through the intrinsic pathway mediated by Bcl2 family members, cytochrome c, Apaf-1 and caspase-9, and extrinsic pathway via death receptors and caspase-8. These data indicate that binding regions shared by VEGF family members may be important in developing novel pan-VEGFR inhibitors that are highly relevant in the pathogenesis of angiogenesis-related diseases.

GSK3β regulatory role is mediated by the reperfusion injury salvage kinase (RISK) pathway, and its inhibition by Akt activation blocks mitochondrial permeability transition pore (mPTP) opening and enhances myocardial survival. The present article discusses the involvement of the PI3K/Akt/GSK3β pathway in cardioprotective effects of natural products against MIRI.

P1, N=83, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2023 --> Jan 2024

NEAT2 downregulation inhibited cell proliferation and EMT through VEGFB and TGF-β/Smad3 pathway in vitro, disclosing a new regulatory mechanism in OSCC. In addition, downregulation of NEAT2 could inhibit the tumor growth and metastasis.

To conclude, TARDBP was found to regulate the alternative splicing of VEGF via SRSF1, induce the formation of VEGF but inhibit that of VEGFb, and promote OC angiogenesis. Hence, TARDBP can serve as an independent prognostic factor and new target for OC cancer therapy.

P2, N=19, Active, not recruiting, Dana-Farber Cancer Institute | N=43 --> 19 | Trial completion date: Dec 2021 --> Dec 2022

In addition, it reduced the metastatic capacity in a 4T1 breast cancer model in vivo. Collectively, our conclusions reveal that Russelioside A is an attractive natural compound for treating triple-negative breast cancer growth and metastasis through regulating NF-κB activation.

There is a significant difference in overall survival between HCC patients with high and low expression of ANGPT2, PGF, VEGFA, and VEGFD. Disease free survival (DFS) is significantly shorter in HCC patients with high ANGPT2, PGF, and VEGFA expression than in those with low ANGPT2, PGF, and VEGFA expression.

Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.

In addition, the developed phage-based EIS immunosensor was applied to satisfactorily detect VEGF165 in human serum samples. Considering its ultra-sensitivity, good selectivity, batch reproducibility and stability, the screened selective phage-based EIS sensor is envisioned potential application in diagnosis and therapy.

Enhanced therapeutic efficacy was achieved when two agents ([Lu]Lu-cG250 RIT and sunitinib) that on their own did not induce satisfactory response levels, are combined. Our findings provide a promising new therapeutic strategy for patients with advanced RCC.

However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group (R=0.509 7). Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.

Free aflibercept in excess of the VEGF-bound form was not maintained at this dose level. The dose limiting toxicity (DLT) of aflibercept combined with docetaxel was febrile neutropenia, which occurred in 2 of 3 Japanese patients at the lowest aflibercept dose level (2 mg/kg) combined with docetaxel (60 mg/m) and therapeutic G-CSF use. A recommended dose for further studies was not determined because of the DLT at the starting dose.

TNFSF11 (or RANKL) shows high expression in CAFs and osteoblastic OS cells in OS, and osteoblasts in GCTB. This study investigates pro-angiogenic genes in GCTB and OS and suggests that these genes and their expression patterns are cell-type specific and could provide potential prognostic biomarkers and cell type target treatment for GCTB and OS.

The angiogenic characteristics of meningiomas may be suppressed by using antiangiogenic drugs to prevent neovascularization, thus improving prognosis.

Taken together, the above data indicates that XIST serves as an oncogenic factor to enhance the growth and invasion of OSCC cells by targeting the miR-133a/VEGFB axis.

In a phase II window study of Olaparib alone or with Cisplatin or with Durvalumab or no treatment, we performed transcriptomic profiling to evaluate the modulation of tumor microenvironment post- treatment. Conclusions Our results uncover macrophage-mediated immune suppression as a liability of PARP inhibitor treatment. These results are consistent with data showing that targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer.

NDRG1-induced VEGFA exerts protective effects in GBM via the VEGFA/VEGFR2 pathway. Therefore, targeting both NDRG1 and VEGFA may represent a novel therapy for the treatment of GBM.

Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors.

Our data show pathological impairment in angiogenic potential and gene expression in adipose tissue of breast cancer patients in a longitudinal study. These data support our observed defects in MV function (response to FMD and Ach) during and after CTx treatment. We observed significant reductions in MV function and capillary sprouting during treatment with CTx in the absence of a clinically relevant reduction in cardiac function. Our findings suggest that CTx-induced MV dysfunction precedes and may contribute to future adverse CV events.

The combination of ziv-aflibercept and pembrolizumab demonstrated an acceptable safety profile with antitumor activity in solid tumors. The combination is currently being studied in sarcoma and anti-PD-1-resistant melanoma.

Thus, analyses of single lesion may not completely recapitulate genomic features of recurrent ICC. These observations might have considerable implications for targeted treatment approaches as well as in particular for patient selection before surgery.

Many publications already highlighted the importance of VEGF-A and its splice variants in tumor therapy, especially in breast cancer, which are summarized in this review. Furthermore, we were able to demonstrate that cytoplasmatic VEGFA/b expression is higher in invasive breast cancer tumor cells than in normal tissues or stroma. These examples show that the detection of VEGF splice variants can be performed also on the protein level in formalin fixed tissues. Although no quantitative conclusions can be drawn, these results may be the starting point for further studies at a quantitative level, which can be a major step towards the design of targeted antibody-based (breast) cancer therapies.

Using in vitro system, we found that beta8 levels strongly correlated with response to paclitaxel, docetaxel, cisplatin and 5-FU (all r>0.6)... : We were unable to validate the previous reports based on experimental studies that beta8 is associated with angiogenesis and regulatory T-cell infiltration via TGF-beta signaling in multiple large patient cohorts. Beta8 is highly expressed in triple-negative subtype, and WNT/beta-catenin and cell proliferation gene sets were enriched although there was no correlation with neither grade nor Ki67. Beta8 levels was not association with survival, but high beta8 expression was a predictive biomarker for pathological complete response after neoadjuvant chemotherapy in triple-negative breast cancer.

The combination of Alectinib and bevacizumab demonstrated to be a safe and highly effective treatment in terms of response in the first-line setting. Moreover, it seems promising for patients with brain metastases. These results warrant the design of larger confirmatory trials, ideally a randomized phase III study.