Overview
- A Science Translational Medicine study finds that paclitaxel triggers reactive oxygen species in immune cells, activating the IRE1α–XBP1 pathway and provoking inflammation that damages dorsal root ganglia.
- The mechanism localizes to leukocytes rather than neurons, reframing chemotherapy-induced peripheral neuropathy as an immune-driven process.
- In mouse models, genetic deletion of IRE1α in immune cells or treatment with a selective IRE1α inhibitor reduced pain behaviors, preserved nerve fibers, and dampened inflammation.
- In a small pilot cohort of women receiving paclitaxel for gynecologic cancers, heightened IRE1α–XBP1 activation in circulating immune cells appeared before those patients later developed severe neuropathy.
- Because IRE1α inhibitors are already in phase 1 trials for solid tumors, researchers highlight a near-term opportunity to test preventive strategies, noting that the human data are preliminary and require larger validation.