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Bulletin Du Cancer Feb 2017We have just celebrated the 50th anniversary of cisplatin cytotoxic potential discovery. It is time to take stock… and it seems mainly positive. This drug, that... (Review)
Review
We have just celebrated the 50th anniversary of cisplatin cytotoxic potential discovery. It is time to take stock… and it seems mainly positive. This drug, that revolutionized the treatment of many cancer types, continues to be the most widely prescribed chemotherapy. Despite significant toxicities, resistance mechanisms associated with treatment failures, and unresolved questions about its mechanism of action, the use of this cytotoxic agent remains unwavering. The interest concerning this "old" invincible drug has not yet abated. Indeed many research axes are in the news. New platinum salts agents are tested, new cisplatin formulations are developed to target tumor cells more efficiently, and new combinations are established to increase the cytotoxic potency of cisplatin or overcome the resistance mechanisms.
Topics: Antineoplastic Agents; Cisplatin; DNA Adducts; Drug Resistance, Neoplasm; History, 20th Century; History, 21st Century
PubMed: 27989629
DOI: 10.1016/j.bulcan.2016.11.011 -
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 -
Chemico-biological Interactions Dec 2022One of the leading global causes of death is cancer; even though several treatment methods have improved survival rates, the incidence and fatality rates remain high.... (Review)
Review
One of the leading global causes of death is cancer; even though several treatment methods have improved survival rates, the incidence and fatality rates remain high. Naphthoquinones are a type of quinone that is found in nature and has vital biological roles. These chemicals have anticancer (antineoplastic), analgesic, anti-inflammatory, antimalarial, antifungal, antiviral, antitrypanosomal, antischistosomal, leishmanicidal, and anti-ulcerative effects. Direct addition of a substituent group to the 1,4-naphthoquinone ring can alter the naphthoquinone's oxidation/reduction and acid/base characteristics, and the activity can be altered. Because of their pharmacological properties, such as anticancer activity and probable therapeutic application, naphthoquinones have greatly interested the scientific community. Some chemicals having a quinone ring in malignant cells have been found to have antiproliferative effects. Naphthoquinones' deadly impact is connected with the inhibition of electron transporters, the uncoupling of oxidative phosphorylation, the creation of ROS, and the formation of protein adducts, notably with -SH enzyme groups. This review article aims to discuss naphthoquinones and their derivatives, which act against cancer and their future perspectives. This review covers several studies highlighting the potent anticancer properties of naphthoquinones. Further, various proposed mechanisms of anticancer actions of naphthoquinones have been summarized in this review.
Topics: Naphthoquinones; Antineoplastic Agents; Quinones; Oxidation-Reduction; Antimalarials
PubMed: 36179774
DOI: 10.1016/j.cbi.2022.110198 -
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 -
Nanomedicine (London, England) 2015Nanocrystals are carrier-free solid drug particles that are sized in the nanometer range and have crystalline characteristics. Due to high drug loading (as high as 100%)... (Review)
Review
Nanocrystals are carrier-free solid drug particles that are sized in the nanometer range and have crystalline characteristics. Due to high drug loading (as high as 100%) - free of organic solvents or solubilizing chemicals - nanocrystals have become attractive in the field of drug delivery for cancer treatment. Top-down and bottom-up approaches have been developed for preparing anticancer nanocrystals. In this review, preparation methods and in vivo performance of anticancer nanocrystals are discussed first, followed by an introduction of hybrid nanocrystals in cancer theranostics.
Topics: Antineoplastic Agents; Humans; Nanoparticles; Neoplasms; Surface Properties
PubMed: 26293310
DOI: 10.2217/nnm.15.73 -
Histochemistry and Cell Biology Dec 2018As in the systemic treatment of any disease, it is crucial for anti-cancer drugs to reach their target at a sufficient that is a therapeutically effective dose. However,... (Review)
Review
As in the systemic treatment of any disease, it is crucial for anti-cancer drugs to reach their target at a sufficient that is a therapeutically effective dose. However, unlike normal organs, solid tumors have a tendency to be undersupplied and hypoxic. This not only leads to insufficient supply of oxygen and nutrients but also to inefficient transport of drugs into tumors. As a consequence, administered doses have to be raised, resulting in increased side effects and often premature termination of treatment. A better understanding of the mechanisms that hamper transport of drugs into tumors could lead to the development of auxiliary strategies aimed at increasing tumor drug delivery and accumulation and thereby improving the efficacy of anti-cancer drugs at our disposal. The tumor microenvironment (TME), i.e., its vasculature, stroma, extracellular matrix and immune environment affect the transport of drugs to the tumor and their distribution within the tumor tissue in various ways. In this review we will highlight the current research regarding the cellular and molecular mechanisms that remain as an obstacle towards an effective cancer therapy, and also focus on the various strategies to alter the TME to increase tumor drug exposure and thereby treatment efficacy.
Topics: Animals; Antineoplastic Agents; Biological Transport; Humans; Neoplasms; Tumor Microenvironment
PubMed: 30361778
DOI: 10.1007/s00418-018-1744-z -
Organic & Biomolecular Chemistry May 2015In this article strategies for the design and synthesis of natural product analogues are summarized and illustrated with some selected examples. Proven strategies... (Review)
Review
In this article strategies for the design and synthesis of natural product analogues are summarized and illustrated with some selected examples. Proven strategies include diverted total synthesis (DTS), function-oriented synthesis (FOS), biology-oriented synthesis (BIOS), complexity to diversity (CtD), hybrid molecules, and biosynthesis inspired synthesis. The latter includes mutasynthesis, the synthesis of natural products encoded by silent genes, and propionate scanning. Most of the examples from our group fall in the quite general concept of DTS. Thus, in case an efficient strategy to a natural product is at hand, modifications are possible at almost any stage of a synthesis. However, even for compounds of moderate complexity, organic synthesis remains a bottle neck. Unless some method for predicting the biological activity of a designed molecule becomes available, the design and synthesis of natural product analogues will remain what it is now, namely it will largely rely on trial and error.
Topics: Antifungal Agents; Antineoplastic Agents; Biological Products; Drug Design
PubMed: 25829247
DOI: 10.1039/c5ob00169b -
Mini Reviews in Medicinal Chemistry 2017Cancer refers to an assemblage of lethal diseases characterized by abnormal growth of cells. The most celebrated adverse effects accredited to the cytotoxic class of... (Review)
Review
Cancer refers to an assemblage of lethal diseases characterized by abnormal growth of cells. The most celebrated adverse effects accredited to the cytotoxic class of anticancer agents are constructed owing to their inability to differentiate between the abnormally multiplying cancerous cell mass and the rapidly dividing healthy cells of the human body. Consequently, unknown targets chemotherapy for cancer play host to a multitude of adverse effects ranging from nausea, alopecia to torturous ages associated with the current treatment etiquette. Nano-pharmaceuticals constitute the advanced scale drug targeting technologies. Nanoemulsion is an important tool in the nano-technological arena designed for clinical and therapeutic application. Currently among different nano-carriers, nanoemulsions are extensively envisaged as efficient drug delivery systems for the targeted delivery of lipophilic cytotoxic antineoplastic agents. Beauties of nanoemulsion include optical clarity, biocompatibility, non-immunogenic, biodegradable, drug encapsulation, sustained and controlled release, nanometric size, large surface area, ease of preparation and thermodynamic stability. After excessive delving, the research fraternity has acknowledged nanoemulsions as proficient nanocarriers capable of effectively addressing the low bioavailability and noncompliance issues associated with the conventional anticancerous chemotherapeutic dosage forms. This review attempts to shed new light on the current status of nanoemulsion in the cancer therapeutics, and commercial field on the basis of morphology, formulation, characteristics and characterization parameters.
Topics: Antineoplastic Agents; Drug Carriers; Drug Delivery Systems; Emulsions; Humans; Nanoparticles; Neoplasms
PubMed: 26891931
DOI: 10.2174/1389557516666160219122755 -
Environmental Toxicology and Chemistry May 2020Cancer is the second leading cause of death worldwide, with 9.6 million cancer-related deaths in 2018. Cancer incidence has increased over time, and so has the... (Review)
Review
Cancer is the second leading cause of death worldwide, with 9.6 million cancer-related deaths in 2018. Cancer incidence has increased over time, and so has the prescription rate of chemotherapeutic drugs. These pharmaceuticals, known as antineoplastic agents, enter the aquatic environment via human excretion and wastewater. The objectives of the present critical review were to investigate the risk of antineoplastics to aquatic species and to summarize the current state of knowledge regarding their levels in the environment, because many antineoplastics are not adequately removed during wastewater treatment. We conducted 2 separate literature reviews to synthesize data on the global environmental prevalence and toxicity of antineoplastics. The antineoplastics most frequently detected in the environment included cyclophosphamide, ifosfamide, tamoxifen, methotrexate, and 5-fluorouracil; all were detectable in multiple water sources, including effluent and surface waters. These antineoplastics span 3 different mechanistic classes, with cyclophosphamide and ifosfamide classified as alkylating agents, tamoxifen as a hormonal agent, and methotrexate and 5-fluorouracil as antimetabolites. Studies that characterize the risk of antineoplastics released into aquatic environments are scarce. We summarize the biological impacts of the most environmentally prevalent antineoplastics on aquatic organisms and propose an adverse outcome pathway for cyclophosphamide and ifosfamide, 2 widely prescribed drugs with a similar immunotoxic mode of action. Acute and chronic ecotoxicity studies using aquatic models are needed for risk characterization of antineoplastics. Environ Toxicol Chem 2020;39:967-985. © 2020 SETAC.
Topics: Antineoplastic Agents; Aquatic Organisms; Environmental Monitoring; Immunosuppression Therapy; Toxicity Tests; Water Pollutants, Chemical
PubMed: 32266737
DOI: 10.1002/etc.4687 -
Advanced Healthcare Materials Apr 2024As an iron-dependent, non-apoptosis, regulated cell death (RCD) modality, ferroptosis has gained growing attention for cancer therapy. With the development of... (Review)
Review
As an iron-dependent, non-apoptosis, regulated cell death (RCD) modality, ferroptosis has gained growing attention for cancer therapy. With the development of nanomaterials in the biomedical field, ferroptotic cancer nanomedicine is extensively investigated. Amongst various nanomaterials, metal-organic frameworks (MOFs) are hybridized porous materials consisting of metal ions or clusters bridged by organic linkers. The superior properties of MOFs, such as high porosity and cargo loading, ease of surface modification, and good biocompatibility, make them appealing in inducing or sensitizing ferroptotic cell death. There are remarkable achievements in the field of MOF-based ferroptosis cancer therapy. However, this topic is not reviewed. This review will introduce the fundamentals of MOF and ferroptosis machinery, summarize the recent progress of MOF-based ferroptotic anticancer drug delivery, discuss the benefits and problems of MOFs as vehicles and sensitizers for cancer ferroptosis, and provide the perspective on future research direction on this promising field.
Topics: Metal-Organic Frameworks; Humans; Ferroptosis; Nanomedicine; Neoplasms; Antineoplastic Agents; Animals; Drug Delivery Systems
PubMed: 38221753
DOI: 10.1002/adhm.202303533