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International Journal of Molecular... Oct 2018Cancer represents a group of heterogeneous diseases characterized by uncontrolledgrowth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a... (Review)
Review
Cancer represents a group of heterogeneous diseases characterized by uncontrolledgrowth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significantrole in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Someof the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeuticwindow and undesired side effects of available anticancer drugs and the limitations of anticancerdrugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranosticcarriers, liposomes, carbon nanotubes, quantum dots, polymeric micelles, dendrimers and metallicnanoparticles. However, nonbiodegradable nanoparticles causes high tissue accumulation andleads to toxicity. MDR is considered a major impediment to cancer treatment due to metastatictumors that develop resistance to chemotherapy. MDR contributes to the failure of chemotherapiesin various cancers, including breast, ovarian, lung, gastrointestinal and hematological malignancies.Moreover, the therapeutic efficiency of anticancer drugs or nanoparticles (NPs) used alone is lessthan that of the combination of NPs and anticancer drugs. Combination therapy has long beenadopted as the standard first-line treatment of several malignancies to improve the clinical outcome.Combination therapy with anticancer drugs has been shown to generally induce synergistic drugactions and deter the onset of drug resistance. Therefore, this review is designed to report andanalyze the recent progress made to address combination therapy using NPs and anticancer drugs.We first provide a comprehensive overview of the angiogenesis and of the different types of NPscurrently used in treatments of cancer; those emphasized in this review are liposomes, polymericNPs, polymeric micelles (PMs), dendrimers, carbon NPs, nanodiamond (ND), fullerenes, carbonnanotubes (CNTs), graphene oxide (GO), GO nanocomposites and metallic NPs used forcombination therapy with various anticancer agents. Nanotechnology has provided the convenienttools for combination therapy. However, for clinical translation, we need continued improvementsin the field of nanotechnology.
Topics: Animals; Antineoplastic Agents; Drug Therapy, Combination; Humans; Nanoparticles
PubMed: 30347840
DOI: 10.3390/ijms19103264 -
ACS Chemical Biology Jan 2013Topoisomerases are ubiquitous enzymes that control DNA supercoiling and entanglements. They are essential during transcription and replication, and topoisomerase... (Review)
Review
Topoisomerases are ubiquitous enzymes that control DNA supercoiling and entanglements. They are essential during transcription and replication, and topoisomerase inhibitors are among the most effective and most commonly used anticancer and antibacterial drugs. This review consists of two parts. In the first part ("Lessons"), it gives background information on the catalytic mechanisms of the different enzyme families (6 different genes in humans and 4 in most bacteria), describes the "interfacial inhibition" by which topoisomerase-targeted drugs act as topoisomerase poisons, and describes clinically relevant topoisomerase inhibitors. It generalizes the interfacial inhibition principle, which was discovered from the mechanism of action of topoisomerase inhibitors, and discusses how topoisomerase inhibitors kill cells by trapping topoisomerases on DNA rather than by classical enzymatic inhibition. Trapping protein-DNA complexes extends to a novel mechanism of action of PARP inhibitors and could be applied to the targeting of transcription factors. The second part of the review focuses on the challenges for discovery and precise use of topoisomerase inhibitors, including targeting topoisomerase inhibitors using chemical coupling and encapsulation for selective tumor delivery, use of pharmacodynamic biomarkers to follow drug activity, complexity of the response determinants for anticancer activity and patient selection, prospects of rational combinations with DNA repair inhibitors targeting tyrosyl-DNA-phosphodiesterases 1 and 2 (TDP1 and TDP2) and PARP, and the unmet need to develop inhibitors for type IA enzymes.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Drug Delivery Systems; Humans; Molecular Structure; Topoisomerase Inhibitors
PubMed: 23259582
DOI: 10.1021/cb300648v -
Metal Ions in Life Sciences Feb 2018Zinc is an important element that is gaining momentum as a potential target for cancer therapy. In recent years zinc has been accepted as a second messenger that is now... (Review)
Review
Zinc is an important element that is gaining momentum as a potential target for cancer therapy. In recent years zinc has been accepted as a second messenger that is now recognized to be able to activate many signalling pathways within a few minutes of an extracellular stimulus by release of zinc(II) from intracellular stores. One of the major effects of this store release of zinc is to inhibit a multitude of tyrosine phosphatases which will prevent the inactivation of tyrosine kinases and hence, encourage further activation of tyrosine kinasedependent signalling pathways. Most of these signalling pathways are not only known to be involved in driving aberrant cancer growth, they are usually the main driving force. All this data together now positions zinc and zinc signalling as potentially important new targets to prevent aggressive cancer growth.
Topics: Animals; Antineoplastic Agents; Cation Transport Proteins; Drug Design; Homeostasis; Humans; Molecular Targeted Therapy; Neoplasms; Signal Transduction; Zinc
PubMed: 29394036
DOI: 10.1515/9783110470734-023 -
Chemical Reviews Jul 2009
Topics: Angiogenesis Inhibitors; Antimetabolites; Antineoplastic Agents; DNA Damage; DNA Topoisomerases; Humans; Neoplasms; Topoisomerase Inhibitors
PubMed: 19583428
DOI: 10.1021/cr900208x -
Pharmacological Reviews Oct 2019Cancer in children is rare with approximately 15,700 new cases diagnosed in the United States annually. Through use of multimodality therapy (surgery, radiation therapy,... (Review)
Review
Cancer in children is rare with approximately 15,700 new cases diagnosed in the United States annually. Through use of multimodality therapy (surgery, radiation therapy, and aggressive chemotherapy), 70% of patients will be "cured" of their disease, and 5-year event-free survival exceeds 80%. However, for patients surviving their malignancy, therapy-related long-term adverse effects are severe, with an estimated 50% having chronic life-threatening toxicities related to therapy in their fourth or fifth decade of life. While overall intensive therapy with cytotoxic agents continues to reduce cancer-related mortality, new understanding of the molecular etiology of many childhood cancers offers an opportunity to redirect efforts to develop effective, less genotoxic therapeutic options, including agents that target oncogenic drivers directly, and the potential for use of agents that target the tumor microenvironment and immune-directed therapies. However, for many high-risk cancers, significant challenges remain.
Topics: Animals; Antineoplastic Agents; Child; Drug Development; Humans; Neoplasms; Tumor Microenvironment
PubMed: 31558580
DOI: 10.1124/pr.118.016972 -
Drug Discovery Today Aug 2016Self-assembly drug conjugate preparation is a promising approach to improve activity and penetration through physiological barriers of potent small molecules, as well as... (Review)
Review
Self-assembly drug conjugate preparation is a promising approach to improve activity and penetration through physiological barriers of potent small molecules, as well as to reduce any side effects. Drug conjugates can self-assemble in water to form nanoparticles (NPs) that offer several advantages because: (i) they are easy to obtain; (ii) they can reach high local drug concentration in tumor tissues; and (iii) they can reduce the side effects of drugs. All these factors improve drug pharmacokinetic properties. Here, we have reviewed the scope of nanotechnology-based self-assembly drug delivery approaches focusing on prodrugs able to form NPs by self-assembly; we have also summarized the current perspective and challenges facing the successful treatment of cancer.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; Prodrugs
PubMed: 27329268
DOI: 10.1016/j.drudis.2016.06.018 -
International Journal of Molecular... Jun 2022Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed in different solid cancers. In recent years, FAK has been recognized as a new target for the... (Review)
Review
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed in different solid cancers. In recent years, FAK has been recognized as a new target for the development of antitumor agents, useful to contrast tumor development and metastasis formation. To date, studies on the role of FAK and FAK inhibitors are of great interest for both pharmaceutical companies and academia. This review is focused on compounds able to block FAK with different potencies and with different mechanisms of action, that have appeared in the literature since 2017. Furthermore, new emerging PROTAC molecules have appeared in the literature. This summary could improve knowledge of new FAK inhibitors and provide information for future investigations, in particular, from a medicinal chemistry point of view.
Topics: Antineoplastic Agents; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Neoplasms; Protein Kinase Inhibitors
PubMed: 35742823
DOI: 10.3390/ijms23126381 -
Biomedicine & Pharmacotherapy =... Jul 2023Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and... (Review)
Review
Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and medicinal effects, including repression of metastases. High impact studies imply that curcumin can modulate the immune system, independently target various metastatic signalling pathways, and repress migration and invasiveness of cancer cells. This review discusses the potential of curcumin as an antimetastatic agent and describes potential mechanisms of its antimetastatic activity. In addition, possible strategies (curcumin formulation, optimization of the method of administration and modification of its structure motif) to overcome its limitation such as low solubility and bioactivity are also presented. These strategies are discussed in the context of clinical trials and relevant biological studies.
Topics: Humans; Curcumin; Antineoplastic Agents; Neoplasms
PubMed: 37141738
DOI: 10.1016/j.biopha.2023.114758 -
Toxins Jun 2020The level of complexity in a disease like cancer presents a number of challenges for effective treatment development, which require significant innovation to overcome...
The level of complexity in a disease like cancer presents a number of challenges for effective treatment development, which require significant innovation to overcome [...].
Topics: Animals; Antineoplastic Agents; History, 20th Century; History, 21st Century; Humans; Neoplasms; Toxins, Biological
PubMed: 32585926
DOI: 10.3390/toxins12060416 -
Metal Ions in Life Sciences Feb 2018There has been much recent interest in the development of therapeutic transition metal-based complexes in part fueled by the clinical success of the platinum(II)... (Review)
Review
There has been much recent interest in the development of therapeutic transition metal-based complexes in part fueled by the clinical success of the platinum(II) anticancer drug, cisplatin. Yet known platinum drugs are limited by their high toxicity, severe side-effects, and incidences of drug resistance. Organometallic ruthenium-arene complexes have risen to prominence as a pharmacophore due to the success of other ruthenium drug candidates in clinical trials. In this chapter, we highlight higher order multinuclear ruthenium-arene complexes and their respective investigations as chemotherapeutic agents. We discuss their unique structural properties and the associated biochemical evaluation in the context of anticancer drug design. We also review the structural considerations for the design of these scaffolds and new therapeutic applications that are uncovered for this class of complexes.
Topics: Animals; Antineoplastic Agents; Coordination Complexes; Drug Design; Humans; Models, Molecular; Molecular Structure; Neoplasms; Organometallic Compounds; Protein Binding; Ruthenium Compounds; Structure-Activity Relationship
PubMed: 29394025
DOI: 10.1515/9783110470734-012