paclitaxel

Overview

Paclitaxel (brand name Taxol; Wikidata Q423762) is a diterpene natural product and microtubule-stabilizing chemotherapeutic agent originally isolated from the bark of the Pacific yew tree (Taxus brevifolia). Its primary mechanism of action involves binding to the β-tubulin subunit of assembled microtubules, hyperstabilizing the mitotic spindle and thereby arresting dividing cells in the G2/M phase of the cell cycle. Unlike vinca alkaloids, which depolymerize microtubules, paclitaxel locks tubulin polymers in a stabilized state, rendering chromosomal segregation impossible and triggering apoptosis in rapidly proliferating cancer cells. This distinctive mechanism, combined with broad-spectrum antitumor activity across breast, ovarian, lung, and several other malignancies, has established paclitaxel as one of the most widely used cytotoxic agents in oncology.

The drug's clinical utility has been complicated historically by its poor aqueous solubility, necessitating formulation with the surfactant Cremophor EL, which itself is associated with hypersensitivity reactions and altered pharmacokinetics. This limitation has driven substantial innovation in delivery science, including albumin-bound nanoparticle formulations (Nab-Paclitaxel), oral lipid-based preparations, and diverse nanoparticle platforms. Paclitaxel is routinely used in combination regimens — most prominently with carboplatin — for cancers of the breast, ovary, lung, and endometrium, and its role continues to expand through combination with modern immunotherapeutic agents such as pembrolizumab, atezolizumab, bevacizumab, and durvalumab.

Focus of Latest Publications

Recent investigations have focused on overcoming the clinical limitations of paclitaxel—principally its poor water solubility, inadequate tumor accumulation, and development of drug resistance—through advanced delivery systems and rational combination strategies. A dominant theme involves engineering nanoparticle platforms to improve pharmacokinetics and therapeutic efficacy. Studies describe chitosan-based, silk fibroin, cyclodextrin-based, metal-organic framework, and polymer-conjugate nanoparticles designed to achieve sustained and pH- or redox-responsive drug release within tumors. Many of these systems demonstrated significantly enhanced cytotoxicity compared to free paclitaxel; for example, fluorinated chitosan nanocarriers carrying paclitaxel and a photosensitizer achieved IC50 values half those of paclitaxel alone in hepatocellular carcinoma cells, while cyclodextrin-hyaluronic acid nanoparticles showed three-fold greater tumor mass reduction than traditional hydrogels in mice.

Paclitaxel combination chemotherapy has been extensively evaluated in both preclinical and clinical settings. In pancreatic cancer, co-delivery with gemcitabine via nanoparticles suppressed tumor growth and prolonged survival compared to free paclitaxel. In breast cancer, engineered nanoparticles combining paclitaxel with a Padi4 inhibitor and RAGE antagonist counteracted chemotherapy-induced metastasis by suppressing histone citrullination and epithelial-mesenchymal transition markers. Chemo-immunotherapy approaches integrated paclitaxel with immune modulators: nanoparticles co-delivering paclitaxel and the TLR7/8 agonist R848 achieved 93.2% tumor inhibition in mice by inducing immunogenic cell death and dendritic cell maturation. Clinical trials combined paclitaxel with checkpoint inhibitors; a phase II study of pembrolizumab with carboplatin/paclitaxel in melanoma reported 43% overall response rate, though without apparent survival advantage over immunotherapy alone.

At the mechanistic level, studies identified factors that modulate paclitaxel efficacy. CTDSPL2 upregulation conferred paclitaxel resistance in breast cancer through regulation of SCYL1 phosphorylation, while MARCH3 enhanced paclitaxel sensitivity in nasopharyngeal carcinoma by promoting hexokinase 2 ubiquitination and destabilization. In non-small cell lung cancer, computational analysis revealed that synergy with paclitaxel arose when partner drugs disrupted the PI3K/Akt pathway, which modulates tau protein activity. Conversely, natural product ardicrenin demonstrated anti-proliferative potency comparable to paclitaxel against osteosarcoma cells through distinct mechanisms—integrin signaling rather than microtubule stabilization.

Supportive care and alternative formulation strategies addressed paclitaxel's toxicity profile. celecoxib mitigated paclitaxel-induced peripheral neuropathy in rats by downregulating the COX-2/PGE2 pathway in dorsal root ganglia and peripheral nerves, suggesting a therapeutic target for combination studies. An oral formulation (DHP107), designed without Cremophor EL solvent, underwent food-effect evaluation in cancer patients. Biotechnological approaches included engineering Salvia miltiorrhiza hairy roots to produce taxadiene, a paclitaxel precursor, at yields of 65 mg/kg fresh weight, potentially addressing long-term supply challenges for this critical anticancer agent.

Key Publications

• NEWJun Biomedical publication details. (PubMed Database, 2026, PMID 42252614)
• Jun Targeting Cancer Cells With Co(III)-Bipyridyl Complex: A Combined In Vitro and In Silico Study on U87MG and ME-180 Cell Lines. (Chemistry & biodiversity, 2026, PMID 42216859): "In silico toxicological studies demonstrate a safer toxicity profile of CoIII complex than paclitaxel, a clinically approved anticancer drug and comparable to Doxovir, a gold-standard in biologically active CoIII-species."
• May A randomized, open-label, two-way crossover clinical trial to evaluate the food effect on pharmacokinetics and safety of DHP107 in patients with advanced solid tumors: the FEEL study. (Cancer chemotherapy and pharmacology, 2026, PMID 42215716): "The phase 1, randomized, open-label, two-way crossover FEEL study assessed the effect of food on the pharmacokinetics of DHP107, an oral paclitaxel with a novel lipid formulation designed to be systemically absorbed without Cremophor EL, in patients with advanced solid tumors."
• Jun Amphiphilic Glycopolymer Nanoparticles for pH-Responsive Paclitaxel Delivery and Enhanced Efficacy in Pancreatic Ductal Adenocarcinoma Therapy. (ACS applied bio materials, 2026, PMID 42138136): "We developed amphiphilic ABC-type glycopolymer nanoparticles (mPEG-b-PCL-b-PGP) [PCG] for the targeted delivery of paclitaxel (PTX)."
• May Randomised, multicentre phase II study of bevacizumab and paclitaxel induction followed by atezolizumab and nab-paclitaxel in patients with PD-L1-positive metastatic triple-negative breast cancer: protocol for the INDUCE trial (JBCRG-M10). (BMJ open, 2026, PMID 42128502): "Addition of bevacizumab and paclitaxel as induction therapy prior to standard atezolizumab and nab-paclitaxel in patients with programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC) may help to overcome vascular endothelial growth factor-associated resistance mechanisms that limit the immune-mediated antitumour efficacy of atezolizumab and nab-paclitaxel."
• May Uncovering the mechanisms of synergistic drug combinations in non-small cell lung cancer through metagene-based classification. (PloS one, 2026, PMID 42118752): "while the enhanced effects of paclitaxel combinations arise from partner drugs disrupting the PI3K/AKT pathway, which in turn modulates Tau protein activity."
• May Simplified perioperative serplulimab and chemotherapy for resectable squamous NSCLC: a phase II trial with biomarker analysis. (Journal for immunotherapy of cancer, 2026, PMID 42114951): "This exploratory, phase II study investigated the feasibility and efficacy of a four-cycle perioperative regimen combining serplulimab with a taxane (paclitaxel or nab-paclitaxel) and carboplatin in patients with resectable stage II-IIIA sq-NSCLC."
• Jun Development and Characterization of N-Acetylcysteine-Conjugated PAMAM Dendrimers: Biophysical Evaluation of Their Interactions with Proteins and Drug Delivery Applications. (ACS applied bio materials, 2026, PMID 42101951): "The dendrimeric conjugates were further loaded with paclitaxel, and in vitro drug release studies were performed at pH 5.5 and pH 7.4, where the results showed 36.39 ± 3.20% and 28.73 ± 0.83% release for paclitaxel-loaded NG3.0 and NG4.0, respectively, at pH 7.4 after 6 h, while at acidic pH (5.5), 49.31 ± 1.69% and 46.62±0.97% release were reported for paclitaxel-loaded NG3.0 and NG4.0 after 6 h, respectively."
• May Reengineered Albumin-Paclitaxel Nanoparticles Remodeling Tumor Cell Death Pathways for Prevention of Chemotherapy-Induced Breast Cancer Metastasis. (ACS nano, 2026, PMID 42085319): "Despite paclitaxel (PTX) chemotherapy being a cornerstone of treatment, it can paradoxically promote metastasis by facilitating Padi4-mediated nuclear expulsion and triggering the RAGE/ERK pathway."
• May Celecoxib Mitigates Paclitaxel-Induced Peripheral Neuropathy Through Modulation of the COX-2/PGE2 Pathway in Rats. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026, PMID 42048120): "Chemotherapy-induced peripheral neuropathy (CIPN) is a severe paclitaxel-associated adverse effect in cancer treatment."