Nitro-fatty acids: promising agents for the development of new cancer therapeutics

Anti-inflammatory nitro-fatty acids (NO2-FAs) are endogenous and pleiotropic mediators that exert tumor-suppressive effects via a novel mechanism of action by targeting a unique set of tumorigenic target proteins.NO2-FAs are promising tumor-selective antineoplastic agents with a favorable safety profile demonstrated in several preclinical models of disease and human clinical Phase 1 and 2 trials.In preclinical models of colorectal and triple-negative breast cancer, NO2-FA exhibited direct anticancer as well as chemo- and radiosensitizing effects in combination with DNA-damaging therapies by suppressing the 26S proteasome, RAD51, and NF-κB. Nitro-fatty acids (NO2-FAs) are endogenous pleiotropic lipid mediators regarded as promising drug candidates for treating inflammatory and fibrotic diseases. Over the past two decades, the anti-inflammatory and cytoprotective actions of NO2-FAs and several molecular targets have been identified. More recently, preclinical studies have demonstrated their potential as prospective cancer therapeutics with favorable safety and tumor-selective profiles. In this review, we describe the mechanisms of action, with a focus on NO2-FA antineoplastic and chemosensitizing effects. We also address the potential therapeutic applications of endogenous and structurally modified NO2-FAs species in cancer treatment. Nitro-fatty acids (NO2-FAs) are endogenous pleiotropic lipid mediators regarded as promising drug candidates for treating inflammatory and fibrotic diseases. Over the past two decades, the anti-inflammatory and cytoprotective actions of NO2-FAs and several molecular targets have been identified. More recently, preclinical studies have demonstrated their potential as prospective cancer therapeutics with favorable safety and tumor-selective profiles. In this review, we describe the mechanisms of action, with a focus on NO2-FA antineoplastic and chemosensitizing effects. We also address the potential therapeutic applications of endogenous and structurally modified NO2-FAs species in cancer treatment.