Glioma

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Background and Aim: Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) gene, which confers a limited response to standard-of-care treatment with temozolomide (TMZ), resulting in a lower survival. Dianhydrogalactitol (VAL-083) is a novel bi-functional DNA-targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated repair of the O6 guanine alkylator TMZ. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. Subjects and Methods: The study has two parts: part 1 is a dose–escalation and induction format to enroll up to ten patients in which they received VAL-083 at 20, 30, or 40 mg/m² per day for 3 days every 21 days concurrently with standard radiation treatment and VAL-083 for up to eight additional cycles. Part 2 comprises an expansion phase to enroll up to twenty additional patients. This study was performed with approval by the Institutional Review Board of Sun Yat-sen University Cancer Center (B2016-058-01) on January 13, 2017, and registered with the ClinicalTrials.gov (NCT03050736) on February 13, 2017. Results: After completion of dose escalation, VAL-083, 30 mg/m² per day, in combination with radiation therapy, was generally safe and well tolerated. At the cutoff date, 23 patients had been enrolled, 14 of whom had been treated in the expansion phase. Consistent with prior studies, myelosuppression was the most common adverse event. Pharmacokinetic assessment indicated that the levels of VAL-083 were as high in the cerebrospinal fluid as in plasma, 2 h postinfusion. Of the 22 patients who had reached their four precycle magnetic resonance imaging assessments, 12 were assessed with disease progression, with a median progression-free survival of 9.9 (95% confidence interval 7.3–12.0) months for all the patients studied. Conclusion: These preliminary data support VAL-083 as a potentially valuable treatment option for newly diagnosed GBM.

Glioma is the most common primary tumor of the central nervous system. In addition to traditional anticancer drugs, some common nonchemotherapeutic drugs have been considered by some scholars, such as nonsteroidal anti-inflammatory drugs, metformin, and statins. These drugs are often used for the treatment of noncancerous diseases. However, it was found that those drugs could be considered for the clinical treatment of glioma, especially in combination with chemotherapy drugs, which may improve the treatment effect. This process is called “repurposing.” Here, we aim to review these drugs and the literature. These “old drugs” have been used clinically for many years, and their safety and feasibility are high. Such combinations are expected to become a new strategy in chemotherapy for glioma in the clinic.

Glioma is one of the most common primary malignant tumors in the central nervous system and glioblastoma (GBM) is the deadly disease. Excessive angiogenesis and adequate blood supply result in rapid proliferation and invasion in GBM. Therefore, targeting angiogenesis may be an effective way to inhibit glioma progression. Currently, there are two categories in targeting angiogenesis in GBM: vascular endothelial growth factor monoclonal antibody and vascular endothelial growth factor receptor tyrosine kinase inhibitors. Unfortunately, none of these ways yield efficient overall survival improvement in GBM, implying that it is difficult to really block the tumor angiogenesis by blocking a single pathway. Expectantly, there are some clinical trials showing that a combination of antiangiogenesis and immunotherapy may exert synergism on suppressing glioma growth and improving patients' prognosis.

Background and Aim: The immune response to glioma is significantly impaired because of isocitrate dehydrogenase (IDH) mutations. However, the immune reaction to glioma is poorly understood. Materials and Methods: We selected 38 patients with IDH-mutant oligodendroglioma and divided them into low-grade and high-grade groups. Forty healthy people were selected as a control group. Blood samples were collected from the control group and from glioma group patients on the day before surgery and at 3 and 7 days after surgery, and numbers of immune cells were determined. This study was approved by the Institutional Ethics Committee of the Faculty of Medicine at Renmin Hospital of Wuhan University, China (approval No. 2018K-C017) on June 4, 2018. Results: The percentages of CD3+, CD4+, CD4+/CD8+, and CD3− CD19+ B-lymphocytes, and of CD3− CD16+ CD56+ natural killer cells were significantly lower (P < 0.05), and the percentage of CD4+ CD25+ regulatory cells was significantly increased (P < 0.05) in the glioma group compared with the control group. IDH-mutant oligodendroglioma patients with a higher grade of malignancy had lower levels of immune cells preoperatively and postoperatively (P < 0.05), and the levels of immune cells increased following surgery (P < 0.05). Conclusions: IDH-mutant oligodendroglioma patients with high-grade malignancy have a lower number of immune cells in peripheral blood compared with patients with low-grade malignancy. This finding can be used as an effective indicator to evaluate the malignancy and prognosis of IDH-mutant oligodendroglioma and provides a new avenue for the immunotherapy of gliomas.

Online since 6^th Sep 2017.