Anti-VEGFR2 therapy delays growth of preclinical pediatric tumor models and enhances anti-tumor activity of chemotherapy

The cover for issue 53 of Oncotarget features Figure 5, "Preclinical models of Ewing's sarcoma and osteosarcoma respond to DC101 alone and in combination with cytotoxic chemotherapy," by Lowery, et al.

Several pediatric cancer mouse models responded to single agent DC101-mediated VEGFR2 inhibition with tumor growth delay.

The author's data indicate differential efficacy of targeting the VEGFR2 pathway in pediatric models and support the continued evaluation of VEGFR2 inhibition in combination with cytotoxic chemotherapy in multiple pediatric indications.

Dr. Beverly Falcon from the Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA said "Though survival rates for pediatric cancer patients have improved dramatically since the early 1960s, cancer remains the leading cause of disease-related death in children and adolescents."

Inhibition of the VEGF pathway in cancer is thought to not only reduce the total number of vessels to support tumor growth, but also improve the function of vessels within the tumor, thereby more effectively delivering other anti-cancer therapeutics.

Of the multifaceted effects on tumor vessels, the VEGF-A:VEGFR2 signaling axis has been pursued as a therapeutic target in adult solid tumors with approvals across a number of tumor histologies.

Here, they tested ramucirumab or the anti-mouse VEGFR2 antibody DC101 in multiple pediatric cancer cell lines and xenograft mouse models with the goal of identifying specific pediatric indications that may respond to ramucirumab-mediated VEGFR2 inhibition.

The Falcon research team concluded, "Our data demonstrate that VEGFR2 inhibition, either as monotherapy or in combination with chemotherapy, promotes anti-tumor responses in several pediatric cancer models and further supports clinical investigation of ramucirumab in combination with other therapies for pediatric cancer patients."

Full text - https://www.oncotarget.com/article/27148/text/

Correspondence to - Beverly Falcon - falcon_beverly_l@lilly.com

Keywords - angiogenesis, pediatric cancer, VEGFR2, ramucirumab, DC101