doxorubicin
doxorubicin
Overview
Doxorubicin is an anthracycline anticancer drug widely used in chemotherapy for a broad range of malignancies, including breast cancer, lymphoma, sarcoma, leukemia, and other solid tumors. Its principal antitumor activity is associated with DNA intercalation and inhibition of topoisomerase II, leading to DNA damage, impaired replication, and apoptosis. Doxorubicin is also notable for its intrinsic fluorescence, which makes it useful as a model compound in drug-delivery and imaging studies.
Despite its established efficacy, doxorubicin is limited by dose-dependent toxicities, especially cardiotoxicity, and by the emergence of tumor resistance. These limitations have made it a central focus of research in nanomedicine, prodrug design, combination therapy, and mechanistic studies of resistance, oxidative stress, ferroptosis, apoptosis, and tumor microenvironment remodeling.
Focus of Latest Publications
Recent publications continue to use doxorubicin as both a therapeutic benchmark and a formulation target in oncology research. Several studies focused on improving its delivery through nanotechnology and stimulus-responsive systems. Examples include hyaluronic acid-based electro-responsive hydrogels, pH- and glutathione-responsive nanozymes, ROS-responsive nanoparticles, thermosensitive liposomes, and biomimetic carriers. These platforms were designed to increase local drug release in the tumor microenvironment while limiting systemic exposure. Related work used folic acid-targeted PLGA nanoparticles, chondroitin sulfate-functionalized lipid nanoparticles, calcium phosphate lipid nanoparticles, and exosome-based systems to co-deliver doxorubicin with other agents such as Bcl-2 siRNA, nifuroxazide, MnTPP, bufalin, vitamin E, or STING agonists. Across these studies, doxorubicin was commonly paired with targeting ligands or stimuli-responsive linkers to improve tumor accumulation and trigger release under acidic, redox-active, or externally controlled conditions.
A major theme in the recent literature is combination therapy. Doxorubicin was co-formulated or co-administered with cyclophosphamide, vincristine, carboplatin, paclitaxel, cisplatin, temozolomide, olaparib, and other anticancer agents in efforts to improve efficacy or overcome resistance. In breast cancer, doxorubicin was studied in triple-negative breast cancer models, including MDA-MB-231 and MCF-7 breast cancer cells, where it was combined with bufalin, vitamin E, nisin, bakuchiol, or pembrolizumab-containing neoadjuvant regimens. In lymphoma and sarcoma contexts, doxorubicin remained part of standard multi-agent protocols such as Pola-R-CHP, N-AVD, VDC, and Ewing-like regimens. In some studies, doxorubicin served as a comparator to assess the potency of new compounds, including topoisomerase-targeting derivatives, Cdk4 inhibitors, and other experimental anticancer molecules.
Mechanistically, several studies examined doxorubicin-induced cell death pathways and resistance biology. Doxorubicin was linked to immunogenic cell death, apoptosis, ferroptosis, mitotic slippage, and DNA damage responses. Some studies investigated how pulsed electromagnetic fields, nitric oxide-enhanced nanosystems, or engineered bacteria-mediated delivery could potentiate doxorubicin’s effects. Others explored resistance mechanisms, including paxillin-associated doxorubicin resistance, nuclear XIAP-linked chemoresistance, SLC44A4-associated sensitivity to DNA-damaging agents, and tumor endothelial cell reprogramming that reduces doxorubicin efficacy. These findings reinforce doxorubicin’s role as a central probe for studying chemotherapy response and resistance in cancer biology.
Doxorubicin also remained a key subject in toxicity and supportive-care research. Multiple studies addressed doxorubicin-induced cardiotoxicity, cardiomyopathy, neurotoxicity, and endothelial injury. Cardioprotective interventions included carvacrol, Vas2870, and Guizhi Gancao Decoction, with mechanistic attention to Nrf2/KEAP1 signaling, microtubule acetylation, and ferroptosis-related pathways. In non-human and veterinary contexts, doxorubicin was reported as a rescue agent in dogs with presumed neoplastic hemorrhage, underscoring its continued use beyond human oncology. Overall, the recent literature portrays doxorubicin as both a clinically indispensable chemotherapeutic and a versatile experimental tool for developing targeted delivery systems, combination regimens, and toxicity-mitigation strategies.