title: Fasting enhances the response of glioma to chemo- and radiotherapy.
abstract: BACKGROUND
  Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, 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 sensitizing tumor cells to chemotoxicity.
  
  
  RESULTS
  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 tumor progression and survival were measured. Starvation-mimicking conditions sensitized 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, sensitized both subcutaneous and intracranial glioma models to radio-and chemotherapy.
  
  
  CONCLUSIONS
  Starvation-induced cancer sensitization 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.
authors.affiliation: Longevity Institute and Department of Biological Sciences, School of Gerontology, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Fernando
authors.initials: F
authors.lastname: Safdie
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandhorst
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Weijun
authors.initials: W
authors.lastname: Wang
authors.forename: Changhan
authors.initials: C
authors.lastname: Lee
authors.forename: Saewon
authors.initials: S
authors.lastname: Hwang
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chen
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001254:Astrocytoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005215:Fasting; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D049449:Luminescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D051381:Rats; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D003606:Dacarbazine; D000077204:Temozolomide