对血管双重阻塞可抑制肿瘤生长

A novel strategy of blocking the growth of blood vessels¹ with antibodies should result in improved treatment of cancerous tumors. The growth of new blood vessels from pre-existing vasculature（脉管系统） is called angiogenesis（血管生成） . In adults, angiogenesis occurs only during wound healing and menstrual cycling（月经周期） , but is abundant and harmful in cancerous tumors and the old-age eye disease frequently leading to blindness called age-related macular degeneration (AMD). Without the formation of new blood vessels, tumors cannot grow beyond a small size due to lack of oxygen and nutrients³. Inhibition of angiogenesis is used in the treatment of cancer and AMD, but not all cancer patients respond, while others become refractory⁵（难治的） to therapy.

Academy professor Kari Alitalo and co-workers at the University of Helsinki, Finland, have previously⁶ shown that antibodies directed towards vascular⁷ endothelial（内皮的） growth factor receptor (VEGFR)-3, found on the surface of endothelial cells lining⁸ vessels, can inhibit⁴ lymphatic metastasis by 50-70% in preclinical tumor² models. Furthermore, antibodies that inhibited⁹ the growth factor VEGF-C from binding¹⁰ to the VEGFR-3 suppressed angiogenesis. However, the trouble with this type of inhibitors is that they work poorly in high growth factor concentrations, when the growth factor easily outcompetes the inhibitor. Also the delivery of drugs into tumors is hampered¹¹ by erratic¹² blood flow and high tumor pressure, which may prevent sufficient amounts of the inhibitor from reaching its target within the tumor.

The novel type of VEGFR-3 blocking antibody has an unprecedented¹³ mechanism¹⁴ of action, which was effective even at very high concentrations of the VEGF-C growth factor. Importantly, the authors showed that combined use of antibodies blocking growth factor binding VEGFR-3 dimerization provided not only an additive¹⁵, but rather a synergistic（协同的） inhibition.

"The new dimerization（二举作用） inhibitor unveils a biologically meaningful rationale（基本原理） for suppressing angiogenesis in tumors that could outperform traditional competitive inhibitors of angiogenesis in tumor therapy. These findings should translate into improved anti-angiogenic and anti-lymphangiogenic tumor therapies", says Professor Alitalo.