A narrative review of emerging chemoprotective agents for chemotherapy-induced toxicity: nanoformulated natural products, dual COX-2/TNF-α inhibitors, and Nrf2 modulators
Abstract
Background: Chemotherapy-induced toxicity remains a major cause of treatment discontinuation, reduced quality of life, and long-term morbidity in cancer survivors. Established chemoprotective agents (dexrazoxane, mesna, and amifostine) are limited by narrow indications (dexrazoxane: only anthracycline cardiotoxicity), significant adverse effects (amifostine: hypotension in 62%), and lack of efficacy against common toxicities such as peripheral neuropathy.
Objective: This focused review evaluates emerging chemoprotective strategies with preclinical or early clinical data published between 2015 and 2025, with an emphasis on agents that address unmet clinical needs.
Methods: This is a critical narrative review, not a systematic review. A literature search was conducted in PubMed, Scopus, and ClinicalTrials.gov (2015-2025) using keywords including "chemoprotection," "nanoparticle," "curcumin," "resveratrol," "dual COX-2/TNF-α inhibitor," "Nrf2 modulator," and "chemotherapy-induced peripheral neuropathy." Articles were selected based on relevance to chemoprotection, mechanistic clarity, and availability of preclinical or clinical data.
Results: Three major emerging categories were identified: (i) Nanoformulated natural products such as curcumin, resveratrol, luteolin, and naringenin encapsulated in polymeric, lipid, or cyclodextrin-based nanocarriers, demonstrate improved bioavailability and enhanced efficacy in preclinical models though chemoprotection-specific clinical data…
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