Glioblastoma chemotherapeutic agents used in the clinical setting and in clinical trials: Nanomedicine approaches to improve their efficacy

Aparicio-Blanco, Juan; Sanz-Arriazu, Lorena; Lorenzoni, Ricardo; Blanco-Prieto, María J.

doi:10.1016/j.ijpharm.2020.119283

Cited by 38 publications

(31 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, inhibitors such as bafilomycin A1 or beclin 1 and ATG5 shRNAs also sensitize GSCs to radiation and reduce their viability and capacity to form neurospheres [134,189]. Likewise, radiation and the inhibition of αv integrin by cilengitide (12), which is currently in clinical evaluation, induce autophagy in GSCs, increasing cytotoxicity and reducing cell survival [190].…”

Section: Current Strategies Targeting Cancer Stem Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The gold standard treatment for GBM patients is surgical resection combined with radiotherapy and adjuvant chemotherapy with the alkylating agent temozolomide (TMZ) [3,12]. Although some molecular features have been proposed as predictive biomarkers of the treatment response to alkylating agents, such as the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter, the clinical utility of these markers is minimal [12,13]. Some reasons proposed for this resistance may include the diffuse infiltrative nature to the surrounding brain, which hinders total resection; the high heterogeneity of GBM, involving distinct molecular pathways; and, more recently, the presence of stem celllike tumorigenic features, including inducing angiogenesis, uncontrolled cellular proliferation, resisting cell death, and genome instability and mutation [3,12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

et al. 2021

View full text Add to dashboard Cite

Glioblastoma (GBM) is the highest-grade form of glioma, as well as one of the most aggressive types of cancer, exhibiting rapid cellular growth and highly invasive behavior. Despite significant advances in diagnosis and therapy in recent decades, the outcomes for high-grade gliomas (WHO grades III-IV) remain unfavorable, with a median overall survival time of 15–18 months. The concept of cancer stem cells (CSCs) has emerged and provided new insight into GBM resistance and management. CSCs can self-renew and initiate tumor growth and are also responsible for tumor cell heterogeneity and the induction of systemic immunosuppression. The idea that GBM resistance could be dependent on innate differences in the sensitivity of clonogenic glial stem cells (GSCs) to chemotherapeutic drugs/radiation prompted the scientific community to rethink the understanding of GBM growth and therapies directed at eliminating these cells or modulating their stemness. This review aims to describe major intrinsic and extrinsic mechanisms that mediate chemoradioresistant GSCs and therapies based on antineoplastic agents from natural sources, derivatives, and synthetics used alone or in synergistic combination with conventional treatment. We will also address ongoing clinical trials focused on these promising targets. Although the development of effective therapy for GBM remains a major challenge in molecular oncology, GSC knowledge can offer new directions for a promising future.

show abstract

Section: Current Strategies Targeting Cancer Stem Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The vast majority of orthotopic xenograft studies have been performed with brain tumor cells. For example, one of the first brain orthotopic studies was carried out by Lal et al, using glioblastoma, the most common and aggressive primary malignancy of the central nervous system, as the tumor model [ 129 ]. The authors performed xenografts both in the yolk sac and in the brain and found important differences in the behavior of the tumor cells.…”

Section: Microenvironmentmentioning

confidence: 99%

Modeling Cancer Using Zebrafish Xenografts: Drawbacks for Mimicking the Human Microenvironment

Cabezas-Sáinz

Pensado‐López

Sáinz

et al. 2020

Cells

View full text Add to dashboard Cite

The first steps towards establishing xenografts in zebrafish embryos were performed by Lee et al., 2005 and Haldi et al., 2006, paving the way for studying human cancers using this animal species. Since then, the xenograft technique has been improved in different ways, ranging from optimizing the best temperature for xenografted embryo incubation, testing different sites for injection of human tumor cells, and even developing tools to study how the host interacts with the injected cells. Nonetheless, a standard protocol for performing xenografts has not been adopted across laboratories, and further research on the temperature, microenvironment of the tumor or the cell–host interactions inside of the embryo during xenografting is still needed. As a consequence, current non-uniform conditions could be affecting experimental results in terms of cell proliferation, invasion, or metastasis; or even overestimating the effects of some chemotherapeutic drugs on xenografted cells. In this review, we highlight and raise awareness regarding the different aspects of xenografting that need to be improved in order to mimic, in a more efficient way, the human tumor microenvironment, resulting in more robust and accurate in vivo results.

show abstract

“…Among the main strategies for tumor treatment, chemotherapy has attracted much attention, because chemotherapy can compensate the shortcomings of surgical tumor treatment, such as tumor recurrent and metastasis. So far, various types of chemotherapeutic agents have been developed and used in clinical settings [ 1 , 2 , 3 ]. However, most chemotherapeutic agents have no inherent tumor targetability, which causes an adverse effect due to a high dose administration.…”

Section: Introductionmentioning

confidence: 99%

Design of a Platelet-Mediated Delivery System for Drug-Incorporated Nanospheres to Enhance Anti-Tumor Therapeutic Effect

Emi

Tabata

2021

Pharmaceutics

View full text Add to dashboard Cite

The objective of this study is to construct a platelet-mediated delivery system for drug-incorporated nanospheres. Nanospheres of poly(lactic-co-glycolic acid) (PLGA-NS) with different sizes and surface properties were prepared by changing the preparation parameters, such as the type of polymer surfactant, the concentration of polymer surfactant and PLGA, and the stirring rate. When incubated with platelets, PLGA-NS prepared with poly(vinyl alcohol) suppressed the platelet activation. Scanning electron microscopic and flow cytometry examinations revealed that platelets associated with PLGA-NS (platelet hybrids, PH) had a similar appearance and biological properties to those of the original platelets. In addition, the PH with PLGA-NS specifically adhered onto the substrate pre-coated with fibrin to a significantly great extent compared with PLGA-NS alone. When applied in an in vitro model of tumor tissue which was composed of an upper chamber pre-coated with fibrin and a lower chamber culturing tumor cells, the PH with PLGA-NS incorporating an anti-tumor drug were delivered to the tumor cells through the specific adhesion onto the upper chamber and, consequently, drug release from the upper chamber took place, resulting in the growth suppression of tumor cells. It is concluded that the drug delivery system based on PH is promising for tumor treatment.

show abstract

Glioblastoma chemotherapeutic agents used in the clinical setting and in clinical trials: Nanomedicine approaches to improve their efficacy

Cited by 38 publications

References 120 publications

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Modeling Cancer Using Zebrafish Xenografts: Drawbacks for Mimicking the Human Microenvironment

Design of a Platelet-Mediated Delivery System for Drug-Incorporated Nanospheres to Enhance Anti-Tumor Therapeutic Effect

Contact Info

Product

Resources

About