Fig. 2

Targeting tumor hypoxia, mitochondrial function, and activating DNA damage pathways via repurposing anti-parasitic drugs. Cancer stem cells (CSCs) are highly dependent on mitochondrial function for propagation and are vital contributors to tumor recurrence, metastasis and resistance to chemo- and radiotherapy. Here, we propose the use of anti-parasitic drugs such as atovaquone, ivermectin, mefloquine, proguanil, and quinacrine to eradicate glioma stem cells (GSCs) and glioma differentiated cells by targeting various cancer metabolic pathways. These drugs alleviate tumor hypoxia and decrease the oxygen consumption rate (OCR) by targeting mitochondrial electron transport chain (ETC) complexes, subsequently inhibiting OXPHOS and enhancing oxidative stress. By decreasing hypoxia, these drugs could potentially increase oxygenation around the tumor tissue. Moreover, these drugs also upregulate mechanisms of DNA damage and tumor suppressor p53. As a consequence, these drugs are proposed to induce apoptosis of GSCs, which, along with an increase in oxygenation (due to reduction in tumor hypoxia), should enhance the radiosensitivity of tumor cells. Combining the anti-parasitic drugs with radiotherapy is therefore an attractive approach to increase oxygen availability and eradicate therapy resistant GSCs and enhance the efficacy of radiotherapy