Diverse microtubule-destabilizing drugs induce equivalent molecular pathway responses in endothelial cells. (PubMed, bioRxiv)
Several MT-destabilizing drugs, including vinblastine, combretastatin A4, and plinabulin, are widely used, or are under evaluation for cancer treatment...To investigate whether differential modulation of molecular pathways might account for clinical differences, we compared gene expression and signaling pathway responses in human pulmonary microvascular endothelial cells (HPMECs), alongside the MT-stabilizing drug docetaxel and the pro-inflammatory cytokine TNF-α...This finding suggests that their distinct clinical effects are not caused by different effects on MTs, but rather by differences in drug transport, pharmacokinetics or tubulin isotype affinity. Our findings provide insights into how plinabulin might protect the bone marrow and may help medicinal chemists design MT drugs for new applications.
