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Prospect and progress of oncolytic viruses for treating peripheral nerve sheath tumors.

ABSTRACT: INTRODUCTION:Peripheral nerve sheath tumors (PNSTs) are an assorted group of neoplasms originating from neuroectoderm and growing in peripheral nerves. Malignant transformation leads to a poor prognosis and is often lethal. Current treatment of PNSTs is predominantly surgical, which is often incomplete or accompanied by significant loss of function, in conjunction with radiotherapy and/or chemotherapy, for which the benefits are inconclusive. Oncolytic viruses (OVs) efficiently kill tumor cells while remaining safe for normal tissues, and are a novel antitumor therapy for patients with PNSTs. AREAS COVERED:Because of the low efficacy of current treatments, new therapies for PNSTs are needed. Pre-clinically, OVs have demonstrated efficacy in treating PNSTs and perineural tumor invasion, as well as safety. We will discuss the various PNSTs and their preclinical models, and the OVs being tested for their treatment, including oncolytic herpes simplex virus (HSV), adenovirus (Ad), and measles virus (MV). OVs can be 'armed' to express therapeutic transgenes or combined with other therapeutics to enhance their activity. EXPERT OPINION:Preclinical testing of OVs in PNST models has demonstrated their therapeutic potential and provided support for clinical translation. Clinical studies with other solid tumors have provided evidence that OVs are safe in patients and efficacious. The recent successful completion of a phase III clinical trial of oncolytic HSV paves the way for oncolytic virotherapy to enter clinical practice.

SUBMITTER: Antoszczyk S

PROVIDER: S-EPMC5111812 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Prospect and progress of oncolytic viruses for treating peripheral nerve sheath tumors.

Antoszczyk Slawomir S Rabkin Samuel D SD

Expert opinion on orphan drugs 20151226 2

<h4>Introduction</h4>Peripheral nerve sheath tumors (PNSTs) are an assorted group of neoplasms originating from neuroectoderm and growing in peripheral nerves. Malignant transformation leads to a poor prognosis and is often lethal. Current treatment of PNSTs is predominantly surgical, which is often incomplete or accompanied by significant loss of function, in conjunction with radiotherapy and/or chemotherapy, for which the benefits are inconclusive. Oncolytic viruses (OVs) efficiently kill tumo ...[more]

PMID: 27867771

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Project description:The characterization of peripheral nerve sheath tumors is challenging. The purpose here was to investigate the diagnostic value of quantitative proton MR spectroscopy at 3T for the characterization of peripheral nerve sheath tumors as benign or malignant, compared with PET.Twenty participants with 24 peripheral nerve sheath tumors underwent MR spectroscopy by use of a point-resolved sequence (TE, 135 ms). Six voxels were placed in 4 histologically proven malignant peripheral nerve sheath tumors and 22 voxels in 20 benign peripheral nerve sheath tumors (9 histologically proven, 11 with documented stability). The presence or absence of a trimethylamine signal was evaluated, the trimethylamine concentration estimated by use of phantom replacement methodology, and the trimethylamine fraction relative to Cr measured. MR spectroscopy results for benign and malignant peripheral nerve sheath tumors were compared by use of a Mann-Whitney test, and concordance or discordance with PET findings was recorded.In all malignant tumors and in 9 of 18 benign peripheral nerve sheath tumors, a trimethylamine peak was detected, offering the presence of trimethylamine as a sensitive (100%), but not specific (50%), marker of malignant disease. Trimethylamine concentrations (2.2 ± 2.8 vs 6.6 ± 5.8 institutional units; P < .049) and the trimethylamine fraction (27 ± 42 vs 88 ± 22%; P < .012) were lower in benign than malignant peripheral nerve sheath tumors. A trimethylamine fraction threshold of 50% resulted in 100% sensitivity (95% CI, 58.0%-100%) and 72.2% (95% CI, 59.5%-75%) specificity for distinguishing benign from malignant disease. MR spectroscopy and PET results were concordant in 12 of 16 cases, (2 false-positive results for MR spectroscopy and PET each).Quantitative measurement of trimethylamine concentration by use of MR spectroscopy is feasible in peripheral nerve sheath tumors and shows promise as a method for the differentiation of benign and malignant lesions. Trimethylamine presence within a peripheral nerve sheath tumor is a sensitive marker of malignant disease, but quantitative measurement of trimethylamine content is required to improve specificity.

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Prospect and progress of oncolytic viruses for treating peripheral nerve sheath tumors.

Publications

Prospect and progress of oncolytic viruses for treating peripheral nerve sheath tumors.

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