Gliomas are the most frequent autochthonous malignant tumours of the human brain (brain cancer). Gliomas are classified into low-grade (slowly growing) or high-grade (fast growing) forms. They typically infiltrate the surrounding brain tissue diffusely at the time when diagnosis is made. Standard therapy consists of surgical resection as far as feasible, to spare functionally important brain areas followed by radiation therapy. To increase overall efficacy, radiation therapy is often combined with adjuvant chemotherapy with temozolomide or other agents.

In spite of such multimodal therapy 2-year survival rates for high grade gliomas (glioblastoma multiforme (GBM), anaplastic astrocytomas, and others, WHO grade III-IV) do not exceed approximately 10-23% in Western countries even under optimum therapy. Complete remission is seen only very rarely. Due to their infiltrative nature curative surgical resection of glioma is only possible in exceptional cases. Disease recurrence is observed in more than 50% of cases within 12 months and in 90% within 24 months. Therapeutic options after recurrence consist of a new resection if anatomically possible, external field irradiation, chemotherapy or palliative experimental methods.

Several problems complicate glioma therapy:
   a) the precise delineation of tumour spread,
   b) the protection of the brain by the blood-brain-barrier (BBB), precluding the
       uptake of most antitumour therapeutics to the brain and
   c) the biological diversity of tumour cells leading to selection of resistant
       sub-clones precluding further therapy.

Inadequate tumour visualization even with modern structural imaging methodologies (contrast enhanced MRI) leads to underestimation of actual tumour spread. Treatment planning for local therapy modalities such as surgery and radiation therapy hence frequently underestimates the affected area, calling for a systemic therapeutic approach.

On the other hand, most systemic anti-cancer treatments like cytotoxic chemotherapeutics or biological agents do not cross the BBB and  consequently have no effect on glioma cells. If reached by therapeutic agents glioma cells are often primarily resistant to pro-apoptotic effects of such medications or quickly develop resistance owing to their high biological diversity.

Best therapeutic results are achieved by multimodal therapeutic strategies combining radiation with chemotherapy and/or radiosensitising agents.

Currently there are no established therapeutic options for patients with low and high grade gliomas recurrent after standard therapy. Improved therapeutic strategies therefore, are urgently required for these patients.

First human treatment experiences with ACD-101 which combines several modes of action in a single molecule have shown encouraging outcomes in different types of this fatal disease.

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