Fasting enhances the response of glioma to chemo and radiotherapy

Glioma, including anaplastic astrocytoma and glioblastoma multiform (GBM) are among the most commonly diagnosed malignant adult brain tumours. GBM is a highly invasive and angiogenic tumour, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitising tumour cells to chemotoxicity.

<strong>Methodology and Principal Findings:</strong> To test the effect of starvation on glioma cells in vitro, we treated primary mouse glia, murine GL26, rat C6 and human U251, LN229 and A172 glioma cells with Temozolomide in ad lib and STS mimicking conditions. In vivo, mice with subcutaneous or intracranial models of GL26 glioma were starved for 48 hours prior to radio-or chemotherapy and the effects on tumour progression and survival were measured. Starvation-mimicking conditions sensitised murine, rat and human glioma cells, but not primary mixed glia, to chemotherapy. In vivo, starvation for 48 hours, which causes a significant reduction in blood glucose and circulating insulin-like growth factor 1 (IGF-1) levels, sensitised both subcutaneous and intracranial glioma models to radio-and chemotherapy.

<strong>Conclusion:</strong> Starvation-induced cancer sensitisation to radio- or chemotherapy leads to extended survival in the in vivo glioma models tested. These results indicate that fasting and fasting-mimicking interventions could enhance the efficacy of existing cancer treatments against aggressive glioma in patients.