Mitochondrial activity inhibitors of cancer-initiating cells and use thereof

An inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle in glioma-initiating cells (GICs) for use in a method for preventing and/or treating tumours presenting glioma-initiating cells (GICs) or presenting glioma-initiating cells from recurrent tumors in a subject who has undergone a prior removal of a tumour glioma bulk, wherein said inhibitor fulfils the following criteria:

• 1) a viability of GICs decreases for more than 50% during the exposure to said inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle during a maximum of 20 days,
• 2) a recovery of GICs is less than 0.2 fold during the recovery phase of a maximum of 20 days, and
• 3) the viability of normal brain cells is sustainable and recoverable during and after the exposure to the said inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle.
• and whereby, said inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle blocks the production of energy by GICs.

A method of preventing and/or treating tumours presenting glioma initiating cells in a subject who has undergone a prior removal of a tumour glioma bulk, wherein preferably said removal of a tumour glioma bulk is segmental resection of a tumour glioma bulk, said method comprises the administration of a therapeutically effective amount of an inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle, wherein said inhibitor fulfils the following criteria:

• 1) a viability of GICs decreases for more than 50% during the exposure to said inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle during a maximum of 20 days,
• 2) a recovery of GICs is less than 0.2 fold during the recovery phase of a maximum of 20 days, and
• 3) the viability of normal brain cells is sustainable and recoverable during and after the exposure to the said inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle,
• and whereby, said inhibitor of the activity of the electron transport chains and/or the mitochondrial TCA cycle blocks the production of energy by GICs.

A kit for screening inhibitors of the activity of the electron transport chains and/or the mitochondrial TCA cycle in glioma-initiating cells (GICs) fulfilling the following criteria:

• 1) a viability of FL1+ cells decreases for more than 50% during the exposure to said inhibitors during a maximum of 20 days,
• 2) a recovery of FL1+ cells is less than 0.2 fold during the recovery phase of a maximum of 20 days, and
• 3) the viability of normal brain cells is sustainable and recoverable during and after the exposure to the said inhibitors,
• and useful in the treatment of tumours presenting glioma initiating cells, wherein said kit comprises primary CIC cultures, primary adherent glioma cells, normal cells and at least one standard inhibitor of the activity of the Complex (I) or Complex (III) of the mitochondrial electron transport chain selected from the group comprising rotenone and antimycin A.