Abstract 4327: Fasting enhances the response of Gl26-glioma to radiation and multiple chemotherapies

Abstract

Abstract Malignant gliomas like anaplastic astrocytoma and glioblastoma mutliforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is highly invasive and angiogenic and causes mortality rates higher than any other brain tumor, resulting in a median survival for GBM patients that is ∼12 to 15 months. Treatment of GBM is multimodal, usually initiated by surgical resection, followed by the adjuvant therapy of radiation and chemotherapy. Temozolomide is the current standard of care for patients with newly diagnosed gliomas and is well tolerated. Temozolomide has been shown to delay tumor-progression and prolong patient survival. As the treatment of GBM remains elusive, the improvement of existing therapies becomes important. The beneficial effects of dietary restriction (DR) on reducing age-dependent diseases, such as cancer, are well established. However, DR is expected to require weeks or even months for efficacy in human patients, which eventually would prove ineffective for cancer patients with fast progressing disease status. We have previously reported that fasting, an intense but brief form of DR differentially protects normal, as opposed to various cancer cells, against the toxicity of high-dose chemotherapy in in-vitro and in-vivo in a neuroblastoma-bearing mice model by causing major changes including the reduction of glucose, and IGF-I. We termed this phenomenon Differential Stress Resistance (DSR). We show that mimicking plasma-fasting conditions in-vitro sensitizes Gl26-glioma cells to chemotherapy treatment by Temozolomide and causes enhanced cell death of the starved glioma cells. We than applied this model of sensitization of cancer cells under fasting conditions to an intracranial and a subcutaneous glioma-tumor model in-vivo. We demonstrate that short term fasting enhances chemo- and radiotherapy in the in-vivo model and prolongs survival of tumor bearing mice even when compared to Temozolomide treated animals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4327. doi:10.1158/1538-7445.AM2011-4327