title: Double autophagy modulators reduce 2-deoxyglucose uptake in sarcoma patients.
abstract: BACKGROUND
  According to the metabolic symbiosis model, cancer stromal fibroblasts could be hijacked by surrounding cancer cells into a state of autophagy with aerobic glycolysis to help provide recycled nutrients. The purpose of this study was to investigate whether combined treatment with the autophagy inhibitor: hydroxychloroquine (HCQ) and the autophagy inducer: sirolimus (rapamycin, Rapa) would reduce glucose utilization in sarcoma patients.
  
  
  METHODS
  Ten sarcoma patients who failed first-line treatment were enrolled in this study. They were treated with 1 mg of Rapa and 200 mg of HCQ twice daily for two weeks. The standardized uptake values (SUV) from pretreatment and posttreatment [18F]-fluorodeoxyglucose positron emission tomography (FDG PET) scans were reviewed, and changes from the baseline SUVmax were evaluated.
  
  
  RESULTS
  Based on FDG PET response criteria, six patients had a partial response; three had stable disease, and one had progressive disease. Nevertheless, none of them showed a reduction in tumor volume. The mean SUVmax reduction in the 34 lesions evaluated was - 19.6% (95% CI = -30.1% to -9.1%), while the mean volume change was +16.4% (95% CI = +5.8% to + 27%). Only grade 1 toxicities were observed. Elevated serum levels of lactate dehydrogenase were detected after treatment in most metabolic responders.
  
  
  CONCLUSIONS
  The results of reduced SUVmax without tumor volume reduction after two weeks of Rapa and HCQ treatment may indicate that non-proliferative glycolysis occurred mainly in the cancer associated fibroblast compartment, and decreased glycolytic activity was evident from Rapa + HCQ double autophagy modulator treatment.
authors.affiliation: Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.|Institue of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsinchu, Taiwan.
authors.forename: Mau-Shin
authors.initials: MS
authors.lastname: Chi
authors.affiliation: Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Su-Chen
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Yang
authors.affiliation: Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Ko
authors.affiliation: Department of Nuclear Medicine and PET Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Yen-Kung
authors.initials: YK
authors.lastname: Chen
authors.affiliation: Institue of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsinchu, Taiwan.
authors.forename: Chen-Han
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Institue of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsinchu, Taiwan.
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Liao
authors.affiliation: Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.|School of Medicine and Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kwan-Hwa
authors.initials: KH
authors.lastname: Chi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D004334:Drug Administration Schedule; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D049268:Positron-Emission Tomography / Q000379:methods; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D019788:Fluorodeoxyglucose F18; D006886:Hydroxychloroquine; D020123:Sirolimus
keywords: hydroxychloroquine; sirolimus; soft tissue sarcoma