Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems

  title={Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems},
  author={Oktay Tacar and Pornsak Sriamornsak and Crispin R. Dass},
  journal={Journal of Pharmacy and Pharmacology},
Objectives  The frontline drug doxorubicin has been used for treating cancer for over 30 years. While providing a cure in select cases, doxorubicin causes toxicity to most major organs, especially life‐threatening cardiotoxicity, which forces the treatment to become dose‐limiting. 
Nucleotropic doxorubicin nanoparticles decrease cancer cell viability, destroy mitochondria, induce autophagy and enhance tumour necrosis
Doxorubicin (Dox) is used clinically against various neoplasias, but suffers from serious side effects, and for the past three decades, this shortcoming has spurred research towards finding better
Doxorubicin-Based Hybrid Compounds as Potential Anticancer Agents: A Review
The hybridization of doxorubicin and other chemotherapeutic drugs is regarded as a promising approach that can lead to effective anticancer agents.
Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use
The mechanisms of biological effects and damage attributed to doxorubicin on mesenchymal stem cells, which are involved in the maintenance and repair of tissues in the body, are explored.
Doxorubicin: Insights into Dynamics, Clinical Uses and Adverse Effects
A mini-review sheds light on DOX including its history, dynamics, clinical uses and adverse effects.
Drug Delivery Approaches for Doxorubicin in the Management of Cancers
The significance of DOX in the form of different delivery approaches in the management of cancers with a reduction in the associated toxicity is described.
Insights into Mechanisms of Doxorubicin Cardiotoxicity
The main goal of the current review is to report the latest findings regarding the mechanisms of doxorubicin-induced cardiotoxicity with respect to free radicals, DNA-damage as well as some other parameters.
Carbon Nanotubes-Doxorubicin Conjugates Molecular Dynamics and Bio-inspired Approaches for Clinical Toxicology
Doxorubicin as a therapeutic drug is used in several human pathologies related to cancer. It has however some side effects that needs to be understood and controlled. This article discusses some
Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
It is shown that delanzomib has antitumor effects and synergizes with doxorubicin (Dox) in human breast cancer cell lines.
Nanomedicine strategies for hematological malignancies: what is next?
This review will discuss the current uses of nanodrugs in hematology, with a focus on the most promising nanoparticles in development for the treatment of hematologic tumors.
Delineating the anti-metastatic potential of pentoxifylline in combination with liposomal doxorubicin against breast cancer cells.


Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice.
Two studies suggest a potentially complementary strategy of rescheduling the administration of classical cytotoxic drugs in order to target tumor endothelial cells, and each presents data suggesting that “metronomic” dosing regimens—either continuous infusion or frequent administration without extended rest periods—could have real value in the clinic.
Molecular biology of doxorubicin-induced cardiomyopathy.
The present article summarizes the unique effect of doxorubicin on cardiac-specific gene expression and agents providing effective cardioprotection.
Pharmacokinetic-Pharmacodynamic Relationships of the Anthracycline Anticancer Drugs
Data indicate that bolus administration, rather than continuous infusion, appears to be an important risk factor for anthracycline-induced cardiomyopathy, thus implying that this type of toxicity is maximum concentration-dependent.
Oncogenes as Novel Targets for Cancer Therapy (Part IV)
This part describes four oncogenes, MDM2, BCL2, XIAP, and Survivin, that are involved in regulation of the cell cycle and apoptosis.
Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity
An overview of issues confirms that anthracyclines remain “evergreen” drugs with broad clinical indications but have still an improvable therapeutic index.
Pegylated liposomal doxorubicin: proof of principle using preclinical animal models and pharmacokinetic studies.
Encapsulation of doxorubicin in polyethylene glycol-coated liposomes (Doxil/Caelyx [PLD], was developed to enhance the safety and efficacy of conventional doxorbicin and has potential applications to treat a variety of cancers.
ABCB8 Mediates Doxorubicin Resistance in Melanoma Cells by Protecting the Mitochondrial Genome
This work prospectively identifies ABCB8 as a specific and major player in the chemoresistance of several melanoma cell lines and provides evidence that ABCB 8 conferred resistance through the protection of mitochondrial DNA from doxorubicin-induced DNA damage.
Anthracyclines in the Treatment of Cancer
Increased distribution in tumours, prolonged circulation and reduced free drug concentrations in plasma may increase antitumour activity and improve the tolerability of the anthracyclines.
A role for ceramide in driving cancer cell resistance to doxorubicin
  • Yong-Yu Liu, Jing Y. Yu, M. Cabot
  • Biology, Materials Science
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2008
For the first time, it is shown that ceramide contributes to cellular resistance to doxorubicin through up‐regulating the gene expression of glucosylceramide synthase (GCS).
Characterization of a novel metabolic strategy used by drug‐resistant tumor cells
  • M. Harper, A. Antoniou, M. Newell
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2002
It is shown that drug‐resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation.