| abstract |
Neuropilin-1 is henceforth a relevant target in cancer treatment, however way-of-action is remains partly elusive and the development of small inhibitory molecules is therefore required for its study. Here, the inventors report that two neuropilin small-sized antagonists (NRPa-47, NRPa-48), VEGF-A165/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in triple negative breast cancer cell line (MDA-MB-231). In particular, the inventors showed for the first time, how NRPa may altered tumor cell signaling and contributed in the down-modulation of the cancer therapeutic key factor p38α-kinase phosphorylation. More importantly, the association of NRPa with a p38α inhibitor leads to additional and/or synergistic effect of these drugs (depending of the dose used) for significantly reducing breast cancer cell proliferation Thus, the efficient association of NRPa and p38α-kinase inhibitors are thus credible for the treatment of cancer. |