taxane

Overview

Taxanes are a class of microtubule-targeting antineoplastic agents used widely in oncology. The best-known members of this family include paclitaxel, docetaxel, and nab-paclitaxel. Their principal pharmacologic action is to promote microtubule stabilization, thereby disrupting normal microtubule dynamics required for mitosis and leading to cell-cycle arrest and apoptosis in rapidly dividing cells. Because of this mechanism, taxanes are commonly used in solid tumors, including breast cancer, pancreatic cancer, prostate cancer, lung cancer, and head and neck malignancies.

In contemporary cancer therapy, taxanes are often combined with other cytotoxic agents, targeted therapies, or immunotherapies to improve response rates and survival. They are also frequently studied in neoadjuvant and induction settings, where they are used before definitive local therapy. Recent research has continued to evaluate taxanes in combination regimens, including carboplatin, trastuzumab-pertuzumab, pembrolizumab, gemcitabine, S-1, and radiotherapy-based protocols, reflecting their central role in multimodal cancer treatment.

Focus of Latest Publications

Recent publications on taxanes have focused on their clinical application in combination with other therapies and the development of novel delivery strategies to enhance efficacy and manage treatment-related toxicity. Clinical studies have evaluated weekly paclitaxel with reduced-dose dexamethasone premedication to minimize steroid-related adverse effects while preventing hypersensitivity reactions, and paclitaxel combined with carboplatin and cetuximab as neoadjuvant therapy for locally advanced head and neck cancer. In pancreatic cancer, nab-paclitaxel combined with S-1 demonstrated a 6-month progression-free survival rate of 71.0% in locally advanced disease, with 18.3% of patients subsequently undergoing surgical resection. Tumor Treating Fields applied concomitantly with gemcitabine and nab-paclitaxel showed significant improvements in overall survival as first-line treatment for unresectable pancreatic adenocarcinoma. Additionally, liposomal doxorubicin with nab-paclitaxel achieved a 90.3% objective response rate in unresectable or recurrent/metastatic adenoid cystic carcinoma of the head and neck, with a median progression-free survival of 25.7 months in patients receiving concurrent chemoradiotherapy.

Mechanistic investigations have revealed several pathways underlying taxane efficacy and resistance across cancer types. paclitaxel combined with sunitinib exhibits synergistic antitumor activity in lung cancer through induction of ferroptosis, a process mediated by concurrent downregulation of ferroptosis suppressors (FTH1, GPX4, SLC7A11) and upregulation of the pro-ferroptotic enzyme ACSL4. paclitaxel predominantly triggers genomic damage with limited reactive oxygen species generation in colorectal cancer models, suggesting a mechanistic profile distinct from platinum-based agents. In prostate cancer, vindoline, a vinca alkaloid, has been identified as an effective ABCB1 modulator capable of restoring docetaxel sensitivity in resistant models by inhibiting drug efflux and enhancing intracellular drug accumulation without altering ABCB1 expression or subcellular localization. Emerging evidence from novel tongue squamous cell carcinoma cell lines derived from non-smoking patients demonstrated that paclitaxel resistance correlates with TP53 mutations and altered gene expression patterns, including increased CCND1 and CCNB1 expression with reduced CDH1 levels.

To overcome solubility, bioavailability, and tumor accumulation limitations, multiple engineered nanoformulations have been developed and evaluated in preclinical models. In triple-negative breast cancer, C-peptide-functionalized solid lipid nanoparticles co-delivering paclitaxel and quercetin demonstrated enhanced tumor targeting via αvβ3 integrin receptors, superior in vivo tumor accumulation by SPECT imaging, and reduced final tumor burdens with minimal systemic toxicity. Exosomal platforms incorporating photothermal agents (polydopamine, BPQDs, or ICG) with paclitaxel achieved substantial tumor reduction and metastasis inhibition, with a single intravenous dose plus near-infrared irradiation converting immunologically "cold" tumors to "hot" tumors and generating long-term memory immunity. Natural extracellular nanovesicles from Taxus leaves, which share plant origin with paclitaxel and contain abundant flavonoids including naringenin, enhanced paclitaxel sensitivity by promoting dendritic cell maturation, enhancing CD8+ T cell infiltration, and depleting regulatory T cells and myeloid-derived suppressor cells. Strain-promoted azide-alkyne cycloaddition chemistry-functionalized microbubbles coupled with ultrasound cavitation-induced sonoporation enhanced paclitaxel payload penetration across endothelial and stromal barriers, resulting in profound tumor regression and prolonged survival in aggressive tumor models. Additionally, hypoxia-responsive paclitaxel prodrugs utilizing 5-nitrofuryl alcohol linkers demonstrated near-complete prodrug reduction under hypoxic conditions, enabling self-amplifying photodynamic-chemotherapy through reactive oxygen species generation that exacerbates hypoxia and triggers sequential paclitaxel release.

Advances in formulation science have further refined taxane delivery through pH- and redox-responsive systems designed to improve therapeutic selectivity and reduce off-target toxicity. Polygonatum sibiricum polysaccharide-based micelles containing docetaxel exhibited rapid disruption under acidic and reductive conditions while maintaining minimal cytotoxicity toward normal cells, significantly enhancing intracellular drug accumulation in cancer cells. Collectively, these studies underscore the continued evolution of taxane-based therapies through optimized premedication regimens to reduce hypersensitivity reactions, rational combination strategies targeting complementary pathways including ferroptosis and immune checkpoint mechanisms, and sophisticated nanoformulation platforms designed to overcome biological barriers and improve therapeutic selectivity.

Key Publications

• NEWJun Reduced-dose dexamethasone premedication for weekly paclitaxel: a retrospective cohort study of early hypersensitivity reactions and steroid-related toxicity. (Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2026, PMID 42371187): "...during weekly paclitaxel chemotherapy."
• NEWJun Novel patient-derived tongue squamous cell carcinoma cell lines from non-smokers: 3D and in vivo models for drug response studies. (Medical oncology (Northwood, London, England), 2026, PMID 42371352): "LMSCC16 also harbored two TP53 mutations and showed increased resistance to Cisplatin and Paclitaxel compared to established TSCC cell lines."
• NEWJul Neoadjuvant Chemotherapy With Paclitaxel, Carboplatin, and Cetuximab for Locally Advanced Head and Neck Cancer. (Anticancer research, 2026, PMID 42373242): "This study evaluated the clinical and pathological responses to neoadjuvant paclitaxel, carboplatin, and cetuximab (PCE) therapy used as a "bridging therapy" to ensure safe transition to surgery."
• NEWJul Magnetic resonance imaging radiomic phenotypes stratify response and define immune states in very high-risk, nonmuscle-invasive bladder cancer treated with tislelizumab plus nanoparticle albumin-bound paclitaxel. (Cancer, 2026, PMID 42339693): "...response to immune checkpoint inhibitor-based therapy."
• NEWJun Nab-paclitaxel plus S-1 induction chemotherapy for patients with locally advanced pancreatic cancer: a multicenter, open-label phase 2 study. (Signal transduction and targeted therapy, 2026, PMID 42324245): "This study aimed to evaluate the efficacy and safety of nab-paclitaxel plus S-1 (SnP) as a first-line treatment in patients with previously untreated LAPC."
• NEWJan Breaking Through the Limits: Nanomedicine at the Service of New Drug Combinations to Tackle Pancreatic Cancer. (Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 2026, PMID 42312894): "Gemcitabine (GEM) monotherapy was the gold standard treatment for PDAC until the early 2010s, when two combinatorial therapies, FOLFIRINOX and GEM combined with Nab-paclitaxel, showed the benefits of the multi-drug approach and became the reference treatments for PDAC."
• NEWJun Exosomes as Biomimetic Nanoplatforms for Synergistic Targeted Chemotherapy and Photothermal Treatment of Breast Cancer. (Journal of biochemical and molecular toxicology, 2026, PMID 42290533): "NIR-activatable photothermal agents (polydopamine, BPQDs, or ICG) are integrated into the membrane and chemotherapeutics or nucleic acids (doxorubicin, paclitaxel, siKRAS, siPD-L1, miR-145) encapsulated in the lumen."
• NEWJun Liposomal doxorubicin plus nab-paclitaxel with/without chemoradiotherapy in head and neck adenoid cystic carcinoma: single-arm phase II study. (Signal transduction and targeted therapy, 2026, PMID 42285940): "Patients received chemotherapeutic nanomedicines (20 mg/m2 liposomal doxorubicin plus 120 mg/m2 nab-paclitaxel on days 1 and 8) for three 21-day cycles."
• NEWJun Design, Synthesis, and Evaluation of Antitumor Activity of Novel Phenylahistin Derivatives with Double F-Substitution via Dual Inhibition of Microtubule and P53/BCL-2/BAX Signaling Pathways. (Journal of medicinal chemistry, 2026, PMID 42273719): "Importantly, compound 45 not only surpassed docetaxel in inhibiting tumor growth in the mouse allograft model using LLC cells but also demonstrated a good safety profile."
• NEWJun Integrin αvβ3-Targeted SLNs for Co-Delivery of Paclitaxel and Quercetin in Triple-Negative Breast Cancer. (ACS applied materials & interfaces, 2026, PMID 42267862): "Although paclitaxel and quercetin (PTX/Q) have been explored as complementary agents, their concurrent use is limited by poor solubility, rapid systemic clearance, and dose-related toxicities."