The key to stopping aggressive cancers could be hitting two targets simultaneously, according to UK research published today.
In a mouse study, researchers from the University of East Anglia (UEA) and the Quadram Institute found they could halt tumour growth when they targeted two signalling switches that trigger the growth of new blood vessels.
They say their findings, published in the latest edition of *Cancer Research Communications*, reveal there could be new approaches for treating cancer in humans.
Tumours grow through angiogenesis and a potential strategy to help slow that down is to disrupt these signalling proteins and the receptors on the cell surface.
However, the clinical benefits are limited unless supplemented by chemotherapy because scientists are unsure of the exact mechanisms by which angiogenesis is controlled.
Researchers have tried to stop vascular endothelial growth factors (VEGFs) co-receptors neuropilin-1 and 2 triggering a cascade of signals within the cell to activate angiogenesis and promising candidates targeting neuropilin-1 have already slowed breast cancer progression in mice.
But there have been few studies targeting both neuropilin-1 and 2 simultaneously.
In this study, Dr Christopher Benwell, a UEA postdoctoral researcher working with Dr Stephen Robinson’s team in the Quadram Institute, studied mice in which the genes for either neuropilin-1 and 2, or both in combination, had been deleted.
In multiple models of cancer, targeting both neuropilin-1 and 2 severely inhibited tumour angiogenesis, cancer growth and metastasis. The extent of the effect was greater than when either one of the receptors was targeted individually.
Dr Benwell said: “We are really excited by these results and have started to delve deeper into the ways these receptors can be manipulated to control angiogenesis in different disease states.”
Further studies in cultured cells suggest that when both neuropilin receptors are targeted, the VEGF receptor is rapidly destroyed by the cell, which cuts off the angiogenic response at its source.
“We are hoping this piece of research will inspire others to consider the impact of targeting multiple proteins to achieve a synergistic anti-cancer response. By doing so, we aim to restrict a cancer’s ability to escape therapy,” added Dr Robinson.
Benwell CJ, Johnson RT, Taylor JAGE et al. Endothelial neuropilin-1 and neuropilin-2 are essential 1 for tumour angiogenesis. *Cancer Research Communications* 13 December 2022; doi: 10.1158/2767-9764.CRC-22-0250
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