ArticleCell death & disease2022
Paclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07109817 (Desloratadine to Prevent Taxane-induced Peripheral Neuropathy in Patients With Breast Cancer), which is not on this map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Desloratadine to Prevent Taxane-induced Peripheral Neuropathy in Patients With Breast Cancer (DETOXp)
Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Paclitaxel Nanomedicines: Molecular Mechanisms of Drug Resistance, Tumor Microenvironment-Responsive Delivery, and Translational Challenges.International journal of molecular sciences · 2026Review
- Potentiating anti-inflammatory and antioxidant effects in vitro: the combined action of zofenoprilat and nebivolol.Pharmacological reports : PR · 2026Article
- Paclitaxel Hypersensitivity: Is Titrated Dosing in Gynecologic Oncology Patients Necessary?Cancers · 2026Article
- Chemotherapy-induced peripheral neuropathy in breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- Multicomponent Reaction-Enabled Semisynthesis of Taxanes Yields an Analogue with Reduced Chemotherapy-Induced Neuropathy.JACS Au · 2025Article
- Distinct safety profiles of albumin-bound nab-paclitaxel and paclitaxel in pancreatic cancer focusing on hematologic and hepatobiliary risks.Scientific reports · 2025Article
- C5a in the peripheral plasma of female fibromyalgia patients is elevated but not related to pain sensitivity as in healthy controls.Scientific reports · 2025Article
- Article
- Quantitation of Plasma Proteins to Predict Taxane-Induced Peripheral Neuropathy.JCO precision oncology · 2025Article
- How to Define and Manage Low-Risk Drug Allergy Labels.The journal of allergy and clinical immunology. In practice · 2024Review
- Molecular and Cellular Involvement in CIPN.Biomedicines · 2024Review
- Complement Receptor C3aR1 Contributes to Paclitaxel-Induced Peripheral Neuropathic Pain in Mice and Rats.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Targeting complement C5a to improve radiotherapy sensitivity in non-small cell lung cancer.Translational lung cancer research · 2023Article
- Recent insights into the mechanisms of anaphylaxis.Current opinion in immunology · 2023Review
- Emerging Approaches for the Management of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Therapeutic Potential of the C5a/C5aR Axis.Pain and therapy · 2022Review
- Therapeutics for Chemotherapy-Induced Peripheral Neuropathy: Approaches with Natural Compounds from Traditional Eastern Medicine.Pharmaceutics · 2022Review
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSRs) are among the most frequent and impairing side effects of the antineoplastic agent paclitaxel. Here, we demonstrated that paclitaxel can bind and activate complement component 5a receptor 1 (C5aR1) and that this binding is crucial in the etiology of paclitaxel-induced CIPN and anaphylaxis. Starting from our previous data demonstrating the role of interleukin (IL)-8 in paclitaxel-induced neuronal toxicity, we searched for proteins that activate IL-8 expression and, by using the Exscalate platform for molecular docking simulations, we predicted the high affinity of C5aR1 with paclitaxel. By in vitro studies, we confirmed the specific and competitive nature of the C5aR1-paclitaxel binding and found that it triggers intracellularly the NFkB/P38 pathway and c-Fos. In F11 neuronal cells and rat dorsal root ganglia, C5aR1 inhibition protected from paclitaxel-induced neuropathological effects, while in paclitaxel-treated mice, the absence (knock-out mice) or the inhibition of C5aR1 significantly ameliorated CIPN symptoms-in terms of cold and mechanical allodynia-and reduced the chronic pathological state in the paw. Finally, we found that C5aR1 inhibition can counteract paclitaxel-induced anaphylactic cytokine release in macrophages in vitro, as well as the onset of HSRs in mice. Altogether these data identified C5aR1 as a key mediator and a new potential pharmacological target for the prevention and treatment of CIPN and HSRs induced by paclitaxel.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.