Paclitaxel-induced adverse effects: insights into multi-organ toxicities and molecular mechanisms

Paclitaxel (PTX), a member of the taxane family of anticancer drugs, is considered one of the most effective chemotherapeutic agents used worldwide. It is widely used in the treatment of solid tumors, including non-small-cell lung, colon, breast, ovarian, prostate, and bladder cancers. Its anticancer activity involves multiple mechanisms: mitotic arrest, mitochondrial damage, and apoptosis induction. Hence, being a non-targeted drug, PTX is associated with many types of toxicities, limiting its effectiveness and affecting the patient's quality of life. Unfortunately, this may result in treatment modifications or even discontinuation. The common clinical toxicities encountered with PTX include cognitive impairment, peripheral neuropathy, testicular toxicity, pulmonary toxicity, cardiotoxicity, hepatotoxicity, and nephrotoxicity. However, the underlying mechanisms of these toxicities remain elusive. This review article focuses on PTX-induced toxicities and the suggested detailed pathological mechanisms underlying each one.