Paclitaxel: What has been done and the challenges remain ahead

Bernabeu, Ezequiel; Cagel, Maximiliano; Lagomarsino, Eduardo; Morettón, Marcela A.; Chiappetta, Diego Andrés

doi:10.1016/j.ijpharm.2017.05.016

Cited by 327 publications

(197 citation statements)

References 161 publications

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“…Polymeric micelles were recently approved by different medicines agencies and are good candidates for solubilizing hydrophobic drugs (notably paclitaxel) without the need for a toxic surfactant. Polymeric micelle formulations of paclitaxel already exist and are used in the clinic (e.g., Genexol-PM®, Samyang-Biopham; Nanoxel-M®, Samyang-Biopham; and Paclical®, Oasmia Pharmaceutical AB) [84].…”

Section: Nanoparticles Based On Polymersmentioning

confidence: 99%

Advances in treatment formulations for acute myeloid leukemia

Briot

Roger

Thépot

et al. 2018

Drug Discovery Today

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Acute myeloid leukemia (AML) is the most common cause of leukemia-related mortality. The combination of cytarabine and anthracycline has been the gold standard of treatment over the past 40 years, but the distribution of the drugs in the body leads to severe adverse effects. Poor prognosis of older patients with AML is the consequence not only of comorbidities, but also of chemoresistance resulting from frequent secondary AML. Numerous strategies using nanotechnologies are in development to improve drug targeting, pharmacokinetics, administration route, chemoresistance, and adverse effects generally observed. Among the four new drugs approved for AML by the US Food and Drug Administration (FDA) in 2017, Vyxeos is a novel liposomal formulation of historical AML drugs. Here, we review current AML treatments and discuss how the development of new formulations will change the therapeutic armamentarium.

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Section: Nanoparticles Based On Polymersmentioning

confidence: 99%

Advances in treatment formulations for acute myeloid leukemia

Briot

Roger

Thépot

et al. 2018

Drug Discovery Today

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show abstract

“…Although paclitaxel, so‐called taxol, has been used for chemotherapy in several cancers including ovarian cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer, and pancreatic cancer and cancer stem cells, its resistance in stem cells and side effects are still hot issues for effective cancer therapy. Hence, new combination therapy with paclitaxel is attractive to overcome its resistance and side effects.…”

Section: Introductionmentioning

confidence: 99%

Melatonin disturbs SUMOylation‐mediated crosstalk between c‐Myc and nestin via MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem cells

Lee

Jung

Shin

et al. 2018

Journal of Pineal Research

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Here the underlying antitumor mechanism of melatonin and its potency as a sensitizer of paclitaxel was investigated in X02 cancer stem cells. Melatonin suppressed sphere formation and induced G2/M arrest in X02 cells expressing nestin, CD133, CXCR4, and SOX-2 as biomarkers of stemness. Furthermore, melatonin reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and upregulated cyclin B1 in X02 cells. Notably, genes of c-Myc related mRNAs were differentially expressed in melatonin-treated X02 cells by microarray analysis. Consistently, melatonin reduced the expression of c-Myc at mRNA and protein levels, which was blocked by MG132. Of note, overexpression of c-Myc increased the expression of nestin, while overexpression of nestin enhanced c-Myc through crosstalk despite different locations, nucleus, and cytoplasm. Interestingly, melatonin attenuated small ubiquitin-related modifier-1 (SUMO-1) more than SUMO-2 or SUMO-3 and disturbed nuclear translocation of nestin for direct binding to c-Myc by SUMOylation of SUMO-1 protein by immunofluorescence and immunoprecipitation. Also, melatonin reduced trimethylated histone H3K4me3 and H3K36me3 more than dimethylation in X02 cells by Western blotting and chromatin immunoprecipitation assay. Notably, melatonin upregulated MT1, not MT2, in X02 cells and melatonin receptor inhibitor luzindole blocked the ability of melatonin to decrease the expression of nestin, p-c-Myc(S62), and c-Myc. Furthermore, melatonin promoted cytotoxicity, sub-G1 accumulation, and apoptotic body formation by Paclitaxcel in X02 cells. Taken together, these findings suggest that melatonin inhibits stemness via suppression of c-Myc, nestin, and histone methylation via MT1 activation and promotes anticancer effect of Paclitaxcel in brain cancer stem cells.

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“…Abraxane, a PTX albumin-based natural polymer, has been approved for clinical use, and other nanoformulations continue to be developed, some of them being evaluated in ongoing clinical trials. 4,99 Docetaxel (DTX), another taxane used as an anticancer drug, is in theory fourfold more potent than PTX but …”

mentioning

confidence: 99%

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Millard¹,

Yakavets²,

Zorin³

et al. 2017

IJN

112

107

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The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS) model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM) components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs) play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a better comprehension of the interactions between NPs and tumor components that affect tumor drug delivery. MCTS is particularly suitable for the high-throughput screening of new nanodrugs.

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Paclitaxel: What has been done and the challenges remain ahead

Cited by 327 publications

References 161 publications

Advances in treatment formulations for acute myeloid leukemia

Advances in treatment formulations for acute myeloid leukemia

Melatonin disturbs SUMOylation‐mediated crosstalk between c‐Myc and nestin via MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem cells

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

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