Double autophagy modulators reduce 2-deoxyglucose uptake in sarcoma patients

Mau Shin Chi, Cheng Yen Lee, Su Chen Huang, Kai Lin Yang, Hui Ling Ko, Yen Kung Chen, Chen Han Chung, Kuang-Wen Liao, Kwan Hwa Chi*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Rationale: 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.

Original languageEnglish
Pages (from-to)29808-29817
Number of pages10
JournalOncotarget
Volume6
Issue number30
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Hydroxychloroquine
  • Sirolimus
  • Soft tissue sarcoma

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