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Journal of Hematology & Oncology May 2020Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand... (Review)
Review
Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to proteasome-mediated degradation. PROTAC complements nucleic acid-based gene knockdown/out technologies for targeted protein reduction and could mimic pharmacological protein inhibition. To date, PROTACs targeting ~ 50 proteins, many of which are clinically validated drug targets, have been successfully developed with several in clinical trials for cancer therapy. This article reviews PROTAC-mediated degradation of critical oncoproteins in cancer, particularly those in hematological malignancies. Chemical structures, cellular and in vivo activities, pharmacokinetics, and pharmacodynamics of these PROTACs are summarized. In addition, potential advantages, challenges, and perspectives of PROTAC technology in cancer therapy are discussed.
Topics: Animals; Antineoplastic Agents; Drug Discovery; Humans; Ligands; Molecular Targeted Therapy; Neoplasms; Proteolysis; Ubiquitination
PubMed: 32404196
DOI: 10.1186/s13045-020-00885-3 -
Therapeutic Drug Monitoring Feb 2020The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized... (Review)
Review
The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized chemotherapy protocols for some types of cancer, protocol changes that usually only occur after large clinical trials demonstrate improvements and individual patients often require dose modifications (amount or interval) or delays in dose administration as toxicities arise. In other areas of medicine, therapeutic drug monitoring is commonly and successfully used to ensure appropriate drug exposure and to limit dose-related toxicities. Currently, the wide pharmacokinetic variability of cytotoxic chemotherapies is addressed clinically by the use of body surface area to determine drug doses; however, this is outdated and demonstrably ineffective for this purpose. This review discusses the challenges of dosing cytotoxic chemotherapies, dose determination strategies for cytotoxic, targeted, and antibody-based biological anticancer drugs, and provides an overview of the recent literature regarding the use of therapeutic drug monitoring in cancer.
Topics: Antineoplastic Agents; Antineoplastic Agents, Immunological; Body Surface Area; Drug Dosage Calculations; Drug Monitoring; Humans; Neoplasms; Pharmacogenomic Variants
PubMed: 31568180
DOI: 10.1097/FTD.0000000000000701 -
Nanomedicine (London, England) Feb 2022Recent studies found that unbalanced copper homeostasis affect tumor growth, causing irreversible damage. Copper can induce multiple forms of cell death, including... (Review)
Review
Recent studies found that unbalanced copper homeostasis affect tumor growth, causing irreversible damage. Copper can induce multiple forms of cell death, including apoptosis and autophagy, through various mechanisms, including reactive oxygen species accumulation, proteasome inhibition, and antiangiogenesis. Hence, copper has attracted tremendous attention and is in the research spotlight in the field of tumor treatment. This review first highlights three typical forms of copper's antitumor mechanisms. Then, the development of diverse biomaterials and nanotechnology allowing copper to be fabricated into diverse structures to realize its theragnostic action is discussed. Novel copper complexes and their clinical applications are subsequently described.
Topics: Antineoplastic Agents; Apoptosis; Autophagy; Cell Line, Tumor; Copper; Humans; Neoplasms; Reactive Oxygen Species
PubMed: 35060391
DOI: 10.2217/nnm-2021-0374 -
Advanced Healthcare Materials Jan 2022Traditional tumor treatments, including chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, are developed and used to treat different types of... (Review)
Review
Traditional tumor treatments, including chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, are developed and used to treat different types of cancer. Recently, chemodynamic therapy (CDT) has been emerged as a novel cancer therapeutic strategy. CDT utilizes Fenton or Fenton-like reaction to generate highly cytotoxic hydroxyl radicals (•OH) from endogenous hydrogen peroxide (H O ) to kill cancer cells, which displays promising therapeutic potentials for tumor treatment. However, the low catalytic efficiency and off-target side effects of Fenton reaction limit the biomedical application of CDT. In this regard, various strategies are implemented to potentiate CDT against tumor, including retrofitting the tumor microenvironment (e.g., increasing H O level, decreasing reductive substances, and reducing pH), enhancing the catalytic efficiency of nanocatalysts, and other strategies. This review aims to summarize the development of CDT and summarize these recent progresses of nanocatalyst-mediated CDT for antitumor application. The future development trend and challenges of CDT are also discussed.
Topics: Antineoplastic Agents; Catalysis; Cell Line, Tumor; Humans; Hydrogen Peroxide; Nanoparticles; Neoplasms; Photochemotherapy; Tumor Microenvironment
PubMed: 34751505
DOI: 10.1002/adhm.202101971 -
Anti-cancer Agents in Medicinal... 2017
Topics: Animals; Antineoplastic Agents; Coordination Complexes; Drug Delivery Systems; Drug Discovery; Heterocyclic Compounds; Humans; Molecular Targeted Therapy; Neoplasms
PubMed: 28143383
DOI: No ID Found -
Pharmaceutical Nanotechnology 2017
Topics: Antineoplastic Agents; Chemistry, Pharmaceutical; Drug Delivery Systems; Humans; Molecular Targeted Therapy; Nanoparticles; Polymers
PubMed: 28948906
DOI: 10.2174/221173850501170316193147 -
Current Medicinal Chemistry 2019
Topics: Antineoplastic Agents; Humans; Immunotherapy; Neoplasms
PubMed: 31526344
DOI: 10.2174/092986732617190820123515 -
Current Drug Targets 2022Spreading rapidly in recent years, cancer has become one of the causes of the highest mortality rates after cardiovascular diseases. The reason for cancer development is... (Review)
Review
Spreading rapidly in recent years, cancer has become one of the causes of the highest mortality rates after cardiovascular diseases. The reason for cancer development is still not clearly understood despite enormous research activities in this area. Scientists are now working on the biology of cancer, especially on the root cause of cancer development. The aim is to treat the cancer disease and thus cure the patients. The continuing efforts for the development of novel molecules as potential anti-cancer agents are essential for this purpose. The main aim of this review was to present a survey on the medicinal chemistry of thioethers and provide practical data on their cytotoxicities against various cancer cell lines. The research articles published between 2001-2020 were consulted to prepare this review article; however, patent literature has not been included. The thioether-containing heterocyclic compounds may emerge as a new class of potent and effective anti-cancer agents in the future.
Topics: Antineoplastic Agents; Heterocyclic Compounds; Humans; Neoplasms; Sulfides
PubMed: 35139780
DOI: 10.2174/1389450122666210614121237 -
Clinical Cancer Research : An Official... Apr 2016
Topics: Antineoplastic Agents; Humans; Immunomodulation; Immunotherapy; Neoplasms
PubMed: 27084737
DOI: 10.1158/1078-0432.CCR-15-1850 -
Molecules (Basel, Switzerland) Feb 2020Cancer is one of the major causes of death worldwide [...].
Cancer is one of the major causes of death worldwide [...].
Topics: Antineoplastic Agents; Biological Products; Humans; Neoplasms
PubMed: 32028725
DOI: 10.3390/molecules25030650