Targeting hypoxia

Treatment activated by low oxygen

Targeting resistant cells in glioblastoma

Glioblastoma (GBM) infiltrates surrounding brain tissue and is difficult to treat.

Within these tumours, an abnormal blood supply can create areas of very low oxygen, known as hypoxia. Cancer cells in these regions can be less responsive to standard treatment and contribute to recurrence.

OncoTherics’ lead clinical asset, AQ4N, uses severe hypoxia to activate an anticancer drug within tumour tissue. This approach is designed to target cells that can survive standard treatment.

Hypoxia activates the treatment

AQ4N is a unidirectional hypoxia-activated prodrug (uHAP): a drug precursor designed to penetrate tumour tissue and undergo irreversible activation in severely hypoxic cancer cells.

Its active form, AQ4, binds to DNA and inhibits topoisomerase II, an enzyme involved in DNA replication. The active drug is retained within cells, helping to concentrate its effects where activation occurs.

Activation demonstrated in patients

AQ4N has demonstrated activation in human tumours, including glioblastoma.

In a published study of 32 patients with solid tumours, including eight with glioblastoma, the active drug AQ4 was detected in every tumour sample analysed. Glioblastoma samples had the highest average AQ4 concentration among the tumour types studied.

These findings provide direct evidence that AQ4N reaches human tumours and is converted into its active form. The study assessed drug activation; clinical benefit requires further evaluation.

Source: Albertella et al., Clinical Cancer Research, 2008.