Advances in the biology and treatment of oligodendrogliomas

Purpose of review: The sensitivity of oligodendroglioma to chemotherapy and the prognostic significance of combined loss of 1p/19q in these tumors are now well established. This review discusses recent molecular, genetic and clinical advances made in studies on oligodendroglioma and mixed oligoastrocytoma. Recent findings: Methylation of genes is a frequent event in oligodendroglioma (OD), but no specific methylation sites have been discovered. In contrast to earlier reports, the expression of the basic helix-loop-helix transcription factors is not specific for OD, but may occur in glial tumors of all lineages. In a number of studies, the prognostic relevance of 1p/19q loss has been confirmed, and several studies have shown that loss of 1p/19q are early events in OD. No candidate genes have so far been identified on 1p36 and 19q13. Gene expression profiling using gene arrays allows the separation of glial tumors according to histology, tumor grade and prognosis. A number of genes have been identified that are significantly more highly expressed in OD. On MRI imaging, OD with combined 1p/19q loss has typical characteristics, including indistinct borders and a mixed signal intensity on T2-weighted images. Despite the large increase in knowledge on the molecular abnormalities in OD, the therapeutic options for these tumors have not improved significantly since the introduction of temozolomide. The increased survival after chemotherapy has been clearly established, but the timing of chemotherapy seems less critical. It is clear that temozolomide is a good alternative to procarbazine, CCNU and vincristine (PCV) chemotherapy, in particular, because it is better tolerated. No randomized trials, however, have compared PCV-chemotherapy to temozolomide. New agents - and probably more targeted therapies - are needed to further improve treatment. Chemo-irradiation deserves further study in anaplastic OD. Summary: The progress in the understanding of genetic and molecular abnormalities of OD has improved the recognition of treatment-sensitive OD, although this has not yet been mirrored in improved therapies or new treatment options. While chemotherapy improves the outcome of OD, further improvements will likely require new drugs or new treatment concepts.

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