Dataset Information

Using Light for Therapy of Glioblastoma Multiforme (GBM).

ABSTRACT: : Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumour with extremely poor prognosis. The current standard of care for newly diagnosed GBM includes maximal surgical resection followed by radiotherapy and adjuvant chemotherapy. The introduction of this protocol has improved overall survival, however recurrence is essentially inevitable. The key reason for that is that the surgical treatment fails to eradicate GBM cells completely, and adjacent parenchyma remains infiltrated by scattered GBM cells which become the source of recurrence. This stimulates interest to any supplementary methods which could help to destroy residual GBM cells and fight the infiltration. Photodynamic therapy (PDT) relies on photo-toxic effects induced by specific molecules (photosensitisers) upon absorption of photons from a light source. Such toxic effects are not specific to a particular molecular fingerprint of GBM, but rather depend on selective accumulation of the photosensitiser inside tumour cells or, perhaps their greater sensitivity to the effects, triggered by light. This gives hope that it might be possible to preferentially damage infiltrating GBM cells within the areas which cannot be surgically removed and further improve the chances of survival if an efficient photosensitiser and hardware for light delivery into the brain tissue are developed. So far, clinical trials with PDT were performed with one specific type of photosensitiser, protoporphyrin IX, which tends to accumulate in the cytoplasm of the GBM cells. In this review we discuss the idea that other types of molecules which build up in mitochondria could be explored as photosensitisers and used for PDT of these aggressive brain tumours.

SUBMITTER: Vasilev A

PROVIDER: S-EPMC7071600 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using Light for Therapy of Glioblastoma Multiforme (GBM).

Vasilev Alex A Sofi Roba R Rahman Ruman R Smith Stuart J SJ Teschemacher Anja G AG Kasparov Sergey S

Brain sciences 20200131 2

<b>:</b> Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumour with extremely poor prognosis. The current standard of care for newly diagnosed GBM includes maximal surgical resection followed by radiotherapy and adjuvant chemotherapy. The introduction of this protocol has improved overall survival, however recurrence is essentially inevitable. The key reason for that is that the surgical treatment fails to eradicate GBM cells completely, and adjacent parenchyma remains ...[more]

PMID: 32024010

Similar Datasets

Project description:Median survival for patients with recurrent GBM is <6 months. Front-line systemic therapy is temozolomide but resistance due to O6-methylguanine-DNA-methyltransferase (MGMT) activity is implicated in poor outcomes. Dianhydrogalactitol (VAL-083) is a structurally unique bi-functional DNA alkylating agent that accumulates in brain tumor tissue. In in vitro studies, VAL-083 demonstrated activity in pediatric and adult GBM cell lines, as well as GBM cancer stem cells. Notably, VAL-083 overcomes resistance to MGMT in vitro. Previous clinical studies suggest that VAL-083 has anti-tumor activity against a range of tumors, including GBM. In light of extensive safety data from clinical trials and promising efficacy in CNS tumors, we initiated a new clinical study to establish the maximum tolerated dose (MTD) and identify a dose and dosing regimen for future efficacy trials in GBM. Early in the development of VAL-083, a cumulative IV dose of 125 mg/m2 delivered in a 35 day cycle in combination with radiation was shown superior to radiation alone in brain cancer (Eagan, et al. 1979). In the present study, the cumulative dose in a 33 day cycle ranges from 9 mg/m2 (cohort 1) to 240 mg/m2 (cohort 7). Six dose cohorts have completed the trial with no drug-related serious adverse events: MTD was not yet reached. Enrollment for cohort 7 (33 day cumulative dose: 240 mg/m2) has been initiated and higher doses may be explored; the results will determine the design of the safety and efficacy registration trial. METHODS: Open-label, single-arm Phase I/II dose-escalation study in patients with histologically-confirmed initial diagnosis of malignant GBM. The study utilizes a 3 + 3 dose-escalation design. Patients receive VAL-083 IV on days 1, 2, and 3 of a 21 day cycle. GBM patients previously been treated with surgery and/or radiation, if appropriate, must have failed both bevacizumab and temozolomide, unless contraindicated. ClinicalTrials.gov Identifier NCT01478178.

Dataset Information

Using Light for Therapy of Glioblastoma Multiforme (GBM).

Publications

Using Light for Therapy of Glioblastoma Multiforme (GBM).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets