Paclitaxel in oncology: balancing anticancer efficacy with potential carcinogenic risks and resistance mechanisms

Paclitaxel is a cornerstone of systemic cancer therapy because of its potent cytotoxic and immunomodulatory properties. By stabilizing microtubules and inducing mitotic arrest, it exerts broad efficacy against breast, ovarian, lung, pancreatic, and other epithelial malignancies. However, its therapeutic impact is limited by multifactorial resistance mechanisms and emerging concerns regarding its potential genotoxicity. The multifactorial resistance is mediated through ABCB1/P-glycoprotein efflux, β-tubulin mutations, apoptotic escape, nuclear envelope stiffening, and tumor microenvironment adaptations, including hypoxia and mechanotransduction. However, its broad utility among various tumors, the potential carcinogenic risk. Major risks are neutropenia, myelosuppression, peripheral neuropathy, arthralgia/myalgia, and hypersensitivity reactions, in addition to reported cases of therapy-related myeloid neoplasms (t-MDS/t-AML) following taxane-containing regimens. To achieve higher responses upon treating with paclitaxel, enhance drug delivery, overcome efflux, and mitigate toxicity, advances in nanoparticles, monitoring, managing risky patients, and perspectives to overcome the resistance have been explored. Paclitaxel exemplifies the therapeutic paradox of chemotherapy-an indispensable agent whose long-term safety and resistance landscape require continued biomarker-guided optimization and precision delivery strategies. This narrative review aims to balance the benefit-to-risk value of paclitaxel through the preclinical and clinical evidence on paclitaxel's dualistic profile, including its antitumor mechanisms, pathways of resistance, and theoretical carcinogenic risks, management of low and high-risk patients, in addition to great future approaches opening more hopes for paclitaxel use in more cancers.