Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives

Seker-Polat, Fidan; Degirmenci, Nareg Pinarbasi; Solaroğlu, İhsan; Bagcı-Önder, Tugba

doi:10.3390/cancers14020443

Cited by 68 publications

(40 citation statements)

References 196 publications

(208 reference statements)

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“…GBM is the most common and malignant primary brain tumor, characterized by high morbidity and poor survival [ 28 ]. Despite advances in diagnosis and treatment, life expectancy remains at approximately 12–18 months [ 1 , 29 ]. Brain invasion, motility, and rapid proliferation are characteristic of GBM cells, and this ability to invade surrounding tissue is a major determinant for malignant tumor progression [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation

Franceschi

Lessi

Morelli

et al. 2022

IJMS

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Glioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative therapies for cancer prevention and treatment. The pentose phosphate pathway (PPP) is a metabolic pathway complementary to glycolysis, and several PPP enzymes have already been demonstrated as potential targets in cancer therapy. In this work, we aimed to evaluate the role of sedoheptulose kinase (SHPK), a key regulator of carbon flux that catalyzes the phosphorylation of sedoheptulose in the nonoxidative arm of the PPP. SHPK expression was investigated in patients with GBM using microarray data. SHPK was also overexpressed in GBM cells, and functional studies were conducted. SHPK expression in GBM shows a significant correlation with histology, prognosis, and survival. In particular, its increased expression is associated with a worse prognosis. Furthermore, its overexpression in GBM cells confirms an increase in cell proliferation. This work highlights for the first time the importance of SHPK in GBM for tumor progression and proposes this enzyme and the nonoxidative PPP as possible therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation

Franceschi

Lessi

Morelli

et al. 2022

IJMS

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“…Focal adhesion kinase (FAK), which is activated by integrin-mediated ECM-adhesion, coordinates integrin signaling and promotes cell migration [ 28 , 29 ]. In addition, FAK expression was found to be correlated to increased invasiveness and recurrence in GBM [ 30 , 31 , 32 ]. These complexes activate intracellular downstream pathways including phosphoinositide-3-kinase (PI3K)/AKT, Src, or Ras mitogen-activated protein kinase (MAPK) pathways [ 33 , 34 ].…”

Section: Role Of Integrin-αvβ3 In Gbm Progressionmentioning

confidence: 99%

Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?

et al. 2022

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Glioblastoma (GBM), the most common primary malignant brain tumor, is associated with a dismal prognosis. Standard therapies including maximal surgical resection, radiotherapy, and temozolomide chemotherapy remain poorly efficient. Improving GBM treatment modalities is, therefore, a paramount challenge for researchers and clinicians. GBMs exhibit the hallmark feature of aggressive invasion into the surrounding tissue. Among cell surface receptors involved in this process, members of the integrin family are known to be key actors of GBM invasion. Upregulation of integrins was reported in both tumor and stromal cells, making them a suitable target for innovative therapies targeting integrins in GBM patients, as their impairment disrupts tumor cell proliferation and invasive capacities. Among them, integrin-αvβ3 expression correlates with high-grade GBM. Driven by a plethora of preclinical biological studies, antagonists of αvβ3 rapidly became attractive therapeutic candidates to impair GBM tumorigenesis. In this perspective, the advent of nuclear medicine is currently one of the greatest components of the theranostic concept in both preclinical and clinical research fields. In this review, we provided an overview of αvβ3 expression in GBM to emphasize the therapeutic agents developed. Advanced current and future developments in the theranostic field targeting αvβ3 are finally discussed.

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“…To date, glioblastoma therapy includes surgical resection of the tumor, radiotherapy, and adjuvant chemotherapy with temozolomide [ 20 ]. However, complete surgical resection of gliomas is extremely difficult, due to local invasion and infiltration of the surrounding tissue; consequently, the tumor recurs causing the death of patients with glioblastoma [ 21 ]. In addition, the existence of the blood–brain barrier (BBB) further reduces the effectiveness of chemotherapy by hindering the delivery of chemotherapeutic agents to the CNS.…”

Section: Introductionmentioning

confidence: 99%

Natural Compounds as Promising Adjuvant Agents in The Treatment of Gliomas

Persano

Gigli

Leporatti

2022

IJMS

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In humans, glioblastoma is the most prevalent primary malignant brain tumor. Usually, glioblastoma has specific characteristics, such as aggressive cell proliferation and rapid invasion of surrounding brain tissue, leading to a poor patient prognosis. The current therapy—which provides a multidisciplinary approach with surgery followed by radiotherapy and chemotherapy with temozolomide—is not very efficient since it faces clinical challenges such as tumor heterogeneity, invasiveness, and chemoresistance. In this respect, natural substances in the diet, integral components in the lifestyle medicine approach, can be seen as potential chemotherapeutics. There are several epidemiological studies that have shown the chemopreventive role of natural dietary compounds in cancer progression and development. These heterogeneous compounds can produce anti-glioblastoma effects through upregulation of apoptosis and autophagy; allowing the promotion of cell cycle arrest; interfering with tumor metabolism; and permitting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis inhibition. Although these beneficial effects are promising, the efficacy of natural compounds in glioblastoma is limited due to their bioavailability and blood–brain barrier permeability. Thereby, further clinical trials are necessary to confirm the in vitro and in vivo anticancer properties of natural compounds. In this article, we overview the role of several natural substances in the treatment of glioblastoma by considering the challenges to be overcome and future prospects.

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Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives

Cited by 68 publications

References 196 publications

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation

Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?

Natural Compounds as Promising Adjuvant Agents in The Treatment of Gliomas

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