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Therapeutic Options for Prostate Cancer: A Contemporary Update
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sakthivel Muniyan, Jawed A. Siddiqui, Surinder K. Batra
Classically, CRPC is managed by chemotherapy as a palliative agent. Until 2004, mitoxantrone was used as a major therapeutic agent. In 2004, docetaxel largely replaced mitoxantrone as the first-line chemotherapeutic agent and showed ~2–4 months of the extended OS. However, since 2010, various new agents have been approved for metastatic castrate-resistant PCa (mCRPC) and these agents changed the treatment landscape significantly. Currently, CRPCa patients may be eligible to receive docetaxel, cabazitaxel, siplucel-T, abiraterone acetate, enzalutamide, apalutamdie, and various experimental agents under clinical trials.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Mitoxantrone is used for the treatment of metastatic breast cancer, adult acute nonlymphocytic leukemia, non-Hodgkin’s lymphoma, and inoperable primary hepatocellular carcinoma. It is administered intravenously and is generally well tolerated, although dose-related cardiotoxicity and myelosuppression are potentially serious side effects. Although cardiotoxicity is less prominent than with the anthracyclines, cardiac examinations and monitoring are still recommended after a certain cumulative dose has been reached.
The Fight Against Cancer
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Mitoxantrone is a synthetic analogue to the anthracyclines, with a similar mechanism of action, used in the treatment of leukaemia and lymphomas predominantly. Its structure is simplified to allow for an uncomplicated synthesis, and lacks the sugar moiety of the anthracyclines, which is thought to cause cardio-toxic side-effects. However, the amino group of the sugar moiety is important for binding, so needed to be replaced by a suitable substituent that would place the required nitrogen in the same relative position. The tetracyclic ring system was truncated by removing the non-planar ring and replacing it with two identical substituents to make the molecule symmetrical and therefore easier to synthesise. The planar tricyclic ring system intercalates the DNA in much the same way as the anthracyclines, with studies of structure-activity relationships revealing the carbonyl and phenol groups to be an important pharmacophore, while the amine nitrogen is crucial for binding. The structures of the anthracycline drug doxorubicin and synthetic analogue mitoxantrone are given in Figure 5 of the Supporting Material∗.
Assessing the risk of multiple sclerosis disease-modifying therapies
Published in Expert Review of Neurotherapeutics, 2019
Xavier Ayrignac, Philippe-Antoine Bilodeau, Alexandre Prat, Marc Girard, Pierre Labauge, Jacques Le Lorier, Catherine Larochelle, Pierre Duquette
Mitoxantrone has been used for a long time to treat patients with aggressive MS. It is an anthracenedione, an intercaling agent with antineoplastic properties, leading to a reduction in lymphocyte proliferation. Common AEs in short duration MS clinical trials included nausea, alopecia, menstrual disorders, urinary tract infections, leucopenia and gamma glutamyl transferase increases (>10%) [97,98]. In real life cohorts, IARs, nausea, transient or persistent amenorrhea and infections were the most common AEs (all > 10%) [99]. The main concern with mitoxantrone is cardiac toxicity and malignancies. Indeed, variable reductions in left ventricular ejection fraction were identified in 2.2%-12% of the treated patients, including congestive heart failure in 0.1%-0.4% [99,100]. Regarding malignancies, if the overall incidence seems low, a significantly increased risk of acute leukemia and perhaps colorectal cancer (respective standardized incidence ratio of 10.44 and 2.98), has been demonstrated [101]. More specifically, between 0.25% and 0.93% (possibly higher risk in patients exposed to >60mg/m2) of exposed patients developed treatment-related acute leukemia.
Modulating acute neuroinflammation in intracerebral hemorrhage: the potential promise of currently approved medications for multiple sclerosis
Published in Immunopharmacology and Immunotoxicology, 2019
Jarred Napier, Lucas Rose, Opeolu Adeoye, Edmond Hooker, Kyle B. Walsh
Mitoxantrone is a synthetic anthraquinone originally designed as an immunosuppressive medication for the treatment of cancer. Its main mechanism of action is through the inhibition of type II topoisomerase [84]. Mitoxantrone has exhibited anti-inflammatory properties by reducing immune cell viability, function, and mobility. Following treatment, MS patients had reduced levels of the chemoattractants CCL5[91] and MMP9 [85] in PBMCs, as well as reduced activation of the chemotaxic factor MCP1 by lipopolysaccharide (LPS) in astrocytes [86]. There was reduced chemotaxis of CD14+ monocytes (10 fold reduction, p= .03) as well as CD4+ and CD8+ T cells [85]. Within one hour of treatment initiation, mitoxantrone reduced the proliferative activity of B cells [87]. Finally, it significantly reduced astrocyte LPS production, resulting in decreased cytotoxic substances and decreased proinflammatory cytokines IL-12, IL-23, and C-reactive protein [86].
Rod-shaped mesoporous silica nanoparticles for nanomedicine: recent progress and perspectives
Published in Expert Opinion on Drug Delivery, 2018
Vu Thanh Cong, Katharina Gaus, Richard D. Tilley, J. Justin Gooding
Mesoporous silica nanorods can also be used to carry various anticancer drugs and nucleic acid. Mitoxantrone is a weakly basic anticancer drug used in treating a variety of cancer types such as breast and prostate cancers. One of the loading methods for mitoxantrone in mesoporous silica relies on the electrostatic interactions between the negative charge of silica and positively charge of mitoxantrone. Wani et al. showed that mesoporous silica nanorods with a dimension of 120 nm x 25 nm could load 34 wt.% of mitoxantrone (34 µg/mg) in phosphate-buffered saline [23]. Unsurprisingly, the release of mitoxantrone from mesoporous silica nanorods was strongly dependent on pH. At pH 7.4, less than 1% of the drug was observed to leak out even after 120 h while 56% of the drug was released at pH 4.5 within an hour. In addition, mesoporous silica nanorods can be used to carry small interfering RNA (siRNA) [78,79]. The main challenge in siRNA delivery is the RNA is easily degraded in the body before it reaches the target tumors. So that a nanoencapsulation is needed [80]. Chen et al. have loaded siRNA to amino-grafted mesoporous silica nanorods with the mesopore size of ~4 nm. A loading efficiency of up to 20 wt.% or 20 mg/g was achieved [81].