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Current Medicinal Chemistry 2009The anthracycline doxorubicin (DOX) is widely used in chemotherapy due to its efficacy in fighting a wide range of cancers such as carcinomas, sarcomas and hematological... (Review)
Review
The anthracycline doxorubicin (DOX) is widely used in chemotherapy due to its efficacy in fighting a wide range of cancers such as carcinomas, sarcomas and hematological cancers. Despite extensive clinical utilization, the mechanisms of action of DOX remain under intense debate. A growing body of evidence supports the view that this drug can be a double-edge sword. Indeed, injury to nontargeted tissues often complicates cancer treatment by limiting therapeutic dosages of DOX and diminishing the quality of patients' life during and after DOX treatment. The literature shows that the heart is a preferential target of DOX toxicity. However, this anticancer drug also affects other organs like the brain, kidney and liver. This review is mainly devoted to discuss the mechanisms underlying not only DOX beneficial effects but also its toxic outcomes. Additionally, clinical studies focusing the therapeutic efficacy and side effects of DOX treatment will be discussed. Finally, some potential strategies to attenuate DOX-induced toxicity will be debated.
Topics: Antibiotics, Antineoplastic; Doxorubicin; Humans; Molecular Conformation; Neoplasms
PubMed: 19548866
DOI: 10.2174/092986709788803312 -
Anti-cancer Agents in Medicinal... 2021Doxorubicin (DOX) is widely used as a clinical first-line anti-cancer drug. However, its clinical application is severely limited due to the lack of tumor specificity of... (Review)
Review
Doxorubicin (DOX) is widely used as a clinical first-line anti-cancer drug. However, its clinical application is severely limited due to the lack of tumor specificity of the drug and severe side effects such as myelosuppression, nephrotoxicity, dose-dependent cardiotoxicity, and multi-drug resistance. To improve the bioavailability of DOX, maximize the therapeutic effect, and reduce its toxicity and side effects, many studies have been done on the nanoformulations of DOX, such as liposomes, polymer micelles, dendrimer, and nanogels. Herein, we review the latest progress of DOX nano-preparations and their anti-tumor effects, hoping to provide theoretical references and new research ideas for the development of new dosage forms of the drug and the technical methods available for clinical application.
Topics: Antibiotics, Antineoplastic; Cell Proliferation; Doxorubicin; Humans; Molecular Conformation; Nanoparticles; Neoplasms
PubMed: 33372884
DOI: 10.2174/1871520621666201229115612 -
Clinical Pharmacokinetics Jul 1988Doxorubicin (adriamycin) has a very wide antitumour spectrum, compared with other anticancer drugs; however, except for Hodgkin's disease, it is not associated with... (Review)
Review
Doxorubicin (adriamycin) has a very wide antitumour spectrum, compared with other anticancer drugs; however, except for Hodgkin's disease, it is not associated with curative chemotherapy. Doxorubicin has been in clinical use for more than 2 decades, and only recently has it been recognised that the cytotoxic effect is produced at the cellular level by multiple mechanisms which have not yet been conclusively identified. Key factors are a combination of doxorubicin-induced free radical formation due to metabolic activation, deleterious actions at the level of the membrane, and drug-intercalation into DNA. Multiple aspects of the clinical pharmacokinetics of this drug have been described. Wide interpatient variations in plasma pharmacokinetics have been noted, but without firm relation to clinical outcome. An apparent volume of distribution of approximately 25 L/kg points to extensive uptake by tissues. Up to several weeks after administration, significant concentrations of doxorubicin have been found in haematopoietic cells and in several other tissues. The maximum cellular doxorubicin concentrations reached in vivo remain significantly below those at which all clonogenic leukaemic cells are killed in vitro. Doxorubicin has been administered as frequent (weekly) low doses, single high doses, and as a continuous infusion. The optimal schedule with respect to tumour cytotoxicity and dose-limiting side effects such as myelosuppression or cardiotoxicity, has never been investigated in a prospective, randomised manner. Clinical trials large enough to study optimal, and possibly individualised, doxorubicin chemotherapy need to be performed. This review summarises pharmacological and pharmacodynamic data of doxorubicin, and discusses these in relation to possible improvement of its therapeutic index. Furthermore, drug interactions, dose-response relationships, mechanisms of action, multidrug resistance, and treatment scheduling are discussed in the perspective of the development of novel treatment strategies.
Topics: Cell Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Drug Interactions; Drug Resistance; Free Radicals; Humans; Neoplasms
PubMed: 3042244
DOI: 10.2165/00003088-198815010-00002 -
Environmental Research Jun 2023Nanomedicine is a field that combines biology and engineering to improve disease treatment, particularly in cancer therapy. One of the promising techniques utilized in... (Review)
Review
Nanomedicine is a field that combines biology and engineering to improve disease treatment, particularly in cancer therapy. One of the promising techniques utilized in this area is the use of micelles, which are nanoscale delivery systems that are known for their simple preparation, high biocompatibility, small particle size, and the ability to be functionalized. A commonly employed chemotherapy drug, Doxorubicin (DOX), is an effective inhibitor of topoisomerase II that prevents DNA replication in cancer cells. However, its efficacy is frequently limited by resistance resulting from various factors, including increased activity of drug efflux transporters, heightened oncogenic factors, and lack of targeted delivery. This review aims to highlight the potential of micelles as new nanocarriers for delivering DOX and to examine the challenges involved with employing chemotherapy to treat cancer. Micelles that respond to changes in pH, redox, and light are known as stimuli-responsive micelles, which can improve the targeted delivery of DOX and its cytotoxicity by facilitating its uptake in tumor cells. Additionally, micelles can be utilized to administer a combination of DOX and other drugs and genes to overcome drug resistance mechanisms and improve tumor suppression. Furthermore, micelles can be used in phototherapy, both photodynamic and photothermal, to promote cell death and increase DOX sensitivity in human cancers. Finally, the alteration of micelle surfaces with ligands can further enhance their targeted delivery for cancer suppression.
Topics: Humans; Micelles; Cell Line, Tumor; Doxorubicin; Hydrogen-Ion Concentration
PubMed: 36948284
DOI: 10.1016/j.envres.2023.115722 -
Molecules (Basel, Switzerland) Jul 2022The scarcity of novel and effective therapeutics for the treatment of cancer is a pressing and alarming issue that needs to be prioritized. The number of cancer cases... (Review)
Review
The scarcity of novel and effective therapeutics for the treatment of cancer is a pressing and alarming issue that needs to be prioritized. The number of cancer cases and deaths are increasing at a rapid rate worldwide. Doxorubicin, an anticancer agent, is currently used to treat several types of cancer. It disrupts myriad processes such as histone eviction, ceramide overproduction, DNA-adduct formation, reactive oxygen species generation, Ca, and iron hemostasis regulation. However, its use is limited by factors such as drug resistance, toxicity, and congestive heart failure reported in some patients. The combination of doxorubicin with other chemotherapeutic agents has been reported as an effective treatment option for cancer with few side effects. Thus, the hybridization of doxorubicin and other chemotherapeutic drugs is regarded as a promising approach that can lead to effective anticancer agents. This review gives an update on hybrid compounds containing the scaffolds of doxorubicin and its derivatives with potent chemotherapeutic effects.
Topics: Antineoplastic Agents; DNA Damage; Doxorubicin; Histones; Humans
PubMed: 35889350
DOI: 10.3390/molecules27144478 -
Journal of Drug Targeting 1996Doxorubicin is a potent antineoplastic agent with activity against numerous human cancers. Encapsulation of doxorubicin inside a liposome alters bioavailability,... (Review)
Review
Doxorubicin is a potent antineoplastic agent with activity against numerous human cancers. Encapsulation of doxorubicin inside a liposome alters bioavailability, biodistribution and thus its biological activity significantly. The physical properties of the liposome (size, lipid components and lipid dose) play a major role in determining drug retention and pharmacokinetics. The therapeutic benefits of liposomal doxorubicin will therefore depend on these physical characteristics. Here we review the toxicity and efficacy of liposomal doxorubicin determined for various liposome compositions (size, lipid composition and drug-to-lipid ratio). These physical properties can be independently varied using the transmembrane pH gradient-dependent drug encapsulation procedure. The results show that the toxicity of the formulation is related to drug retention in the circulation. The antitumor activity is more sensitive to the size of the liposomes. By optimizing these parameters, liposomal doxorubicin formulations can be optimized for improved therapeutic activity.
Topics: Antibiotics, Antineoplastic; Doxorubicin; Drug Carriers; Humans; Hydrogen-Ion Concentration; Liposomes; Neoplasms
PubMed: 8959485
DOI: 10.3109/10611869609015970 -
Current Drug Targets 2018The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the... (Review)
Review
BACKGROUND
The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used clinically as frontline therapy. This same mechanism of cell inhibition is also pertinent to doxorubicin's primary cause of side-effects, that to the cardiac tissue, culminating in such dire events as congestive heart failure. Reactive oxygen species are partly to blame for this effect on the mitochondria, which impact the electron transport chain.
OBJECTIVE
As this review highlights that, there is much more to be learnt about the mitochondria and how it is affected by such effective but toxic drugs as doxorubicin.
CONCLUSION
Such information will aid researchers who search for cancer treatment able to preserve mitochondrial number and function in normal cells.
Topics: Animals; Bone Diseases; Cell Survival; Doxorubicin; Heart Failure; Humans; Mitochondria, Heart; Osteosarcoma; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 25882220
DOI: 10.2174/1389450116666150416115852 -
Bioorganic Chemistry Mar 2022Doxorubicin belongs to the anthracycline chemical class of the drug and is one of the widely used anticancer drugs. The common side effects of doxorubicin include... (Review)
Review
Doxorubicin belongs to the anthracycline chemical class of the drug and is one of the widely used anticancer drugs. The common side effects of doxorubicin include vomiting, hair loss, rashes to serious side-effects such as irreversible cardiotoxicity, and drug-induced leukemia. This led many researchers around the globe to develop methods aimed to achieve higher efficacy and lower toxicity for doxorubicin. The present review article provides a detailed account of the design strategies i.e., chemical modifications and conjugate formation adopted by various research groups to minimize the side effects without compromising with the significant anticancer profile of the drug doxorubicin. Chemical modification of the drug includes alteration at C4' hydroxyl and C3' amine groups present in the sugar part. The pH-sensitive drug delivery system is covered highlighting use of theranostic tantalum oxide to the traditional approach of conjugating with acyl hydrazine and thiourea. Methods adopted to increase the bioavailability of the drugs inside the cancer cells viz., conjugation with humanized monoclonal antibody and other peptides along with their promising results are also discussed. The review further discusses works from recent years comprising of different nanoforms of doxorubicin for the targeted delivery of drugs inside the tumor cells. Few of the articles targeting nucleus or mitochondria as one of the effective cancer treatments are reported. The brain is inaccessible to the drug and it was modified through galactoxyloglucan-modified gold nanocarrier or conjugated with lactoferrin with enhanced permeability through the blood-brain barrier. Prodrug has particularly been used to target tumor tissues without affecting other tissue organs. The present review article offer clear advantages of one method over another adopted to target the cancer cells and may provide an insight for the researchers working in this area.
Topics: Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Galactose; Glucans; Nanoparticles
PubMed: 35030480
DOI: 10.1016/j.bioorg.2022.105599 -
Clinical Journal of Oncology Nursing Jul 1998
Topics: Antineoplastic Agents; Doxorubicin; Drug Interactions; Humans; Nursing Care; Patient Education as Topic
PubMed: 10232157
DOI: No ID Found -
The Western Journal of Medicine Nov 1979Adriamycin (doxorubicin hydrochloride) is an antineoplastic agent effective against a wide range of malignant conditions, although cardiac toxicity, especially... (Review)
Review
Adriamycin (doxorubicin hydrochloride) is an antineoplastic agent effective against a wide range of malignant conditions, although cardiac toxicity, especially dose-dependent cardiomyopathy, limits its long-term use. Previous mediastinal radiation therapy or left ventricular dysfunction and advanced age increase the risk of this complication developing. Unfortunately, there is no readily available, noninvasive method that can predict Adriamycin-induced congestive heart failure (CHF). However, both endomyocardial biopsy and radionuclide ejection-fraction measurement are promising techniques which may soon permit selection of patients who can safely receive this drug. At present, Adriamycin-induced CHF can best be prevented by limiting the total dose as follows: 400 to 450 mg per sq meter following mediastinal radiation and 500 to 550 mg per sq meter for patients without other significant risk factors. Consideration of dose-response data and use of a weekly schedule may soon permit the administration of Adriamycin for long-term antineoplasm therapy.
Topics: Age Factors; Aged; Doxorubicin; Heart Failure; Humans; Neoplasms; Risk
PubMed: 394479
DOI: No ID Found