inflammation<\/a> in mouse models.<\/p>\nFor this study, they used a well-established mouse model that closely reflects the nerve damage experienced by cancer patients.\u00a0They discovered that a commonly-used chemotherapy called paclitaxel can trigger immune cells to produce high levels of reactive oxygen species\u2014molecules that create cellular stress. This stress flips on the IRE1\u03b1 switch, which pushes immune cells into a highly inflammatory state.<\/p>\n
These hyperactive immune cells then travel to the dorsal root ganglia\u2014the sensory nerve clusters that connect the limbs to the spinal cord\u2014and release inflammatory molecules that irritate and damage nerves. This chain reaction produces the hallmark symptoms of CIPN: pain, cold sensitivity and nerve fiber loss.<\/p>\n
Silencing IRE1\u03b1 in immune cells using genetic techniques prevented this inflammatory surge and reduced CIPN-related behaviors in mice. The research team also used a drug that selectively inhibits IRE1\u03b1 and is already in phase 1 clinical trials as a cancer treatment. Mice receiving chemotherapy together with the IRE1\u03b1 inhibitor displayed reduced pain behaviors typically seen after paclitaxel treatment, and their nerves stayed healthier.<\/p>\n
“Our findings suggest that targeting IRE1\u03b1 pharmacologically could mitigate neuropathy induced by taxanes, helping patients continue with their chemotherapy without the negative side effects of nerve damage,” said Dr. Cubillos-Ruiz, who is also co-leader of the Cancer Biology Program at the Sandra and Edward Meyer Cancer Center at Weill Cornell.<\/p>\n
Since IRE1\u03b1 inhibitors are already being evaluated in patients with advanced solid tumors\u2014where abnormal activation of this pathway is known to fuel cancer progression and therapy resistance\u2014the new results raise the possibility that the same drugs could also protect patients from chemotherapy-induced nerve damage.\u00a0According to Dr. Cubillos-Ruiz, such a dual benefit “could meaningfully improve both the effectiveness of cancer treatment and patients’ quality of life.”<\/p>\n
A promising biomarker for patients<\/p>\n
To see how their preclinical findings could translate to patients, the researchers conducted a small pilot study with women receiving paclitaxel for gynecologic cancers. They drew blood before and during each chemotherapy cycle and found that patients who later developed severe CIPN had higher activation of the IRE1\u03b1-XBP1 pathway in their circulating immune cells, even before symptoms appeared.<\/p>\n
This means a blood test might eventually help identify individuals at highest risk of neuropathy, allowing for preventive measures\u2014potentially including IRE1\u03b1 inhibitors\u2014before nerve damage occurs.<\/p>\n
Source:<\/p>\n
Journal reference:<\/p>\n
Fonseca, M. M., et al. (2025). Leukocyte-intrinsic ER stress responses contribute to chemotherapy-induced peripheral neuropathy.\u00a0Science Translational Medicine. doi: 10.1126\/scitranslmed.ady5288.\u00a0https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.ady5288<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Chemotherapy activates a stress sensor in immune cells, triggering inflammation and nerve damage, which may help explain why…\n","protected":false},"author":2,"featured_media":10003,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[4250,2534,4641,2535,134,13346,3193,21696,6918,42820,111,139,69,47040,97878,2850,77585,17561,1518,3405],"class_list":["post-145668","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-blood","tag-cancer","tag-cancer-treatment","tag-chemotherapy","tag-health","tag-inflammation","tag-medicine","tag-nerve","tag-neurons","tag-neuropathy","tag-new-zealand","tag-newzealand","tag-nz","tag-oct","tag-paclitaxel","tag-pain","tag-peripheral-neuropathy","tag-preclinical","tag-research","tag-stress"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/145668","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=145668"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/145668\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/10003"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=145668"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=145668"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=145668"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}