Abstract
<div>Abstract<p><b>Purpose:</b> Dysregulated energetics coupled with uncontrolled proliferation has become a hallmark of cancer, leading to increased interest in metabolic therapies. Glioblastoma (GB) is highly malignant, very metabolically active, and typically resistant to current therapies. Dietary treatment options based on glucose deprivation have been explored using a restrictive ketogenic diet (KD), with positive anticancer reports. However, negative side effects and a lack of palatability make the KD difficult to implement in an adult population. Hence, we developed a less stringent, supplemented high-fat low-carbohydrate (sHFLC) diet that mimics the metabolic and antitumor effects of the KD, maintains a stable nutritional profile, and presents an alternative clinical option for diverse patient populations.</p><p><b>Experimental Design:</b> The dietary paradigm was tested <i>in vitro</i> and <i>in vivo</i>, utilizing multiple patient-derived gliomasphere lines. Cellular proliferation, clonogenic frequency, and tumor stem cell population effects were determined <i>in vitro</i> using the neurosphere assay (NSA). Antitumor efficacy was tested <i>in vivo</i> in preclinical xenograft models and mechanistic regulation via the mTOR pathway was explored.</p><p><b>Results:</b> Reducing glucose <i>in vitro</i> to physiologic levels, coupled with ketone supplementation, inhibits proliferation of GB cells and reduces tumor stem cell expansion. <i>In vivo</i>, while maintaining animal health, the sHFLC diet significantly reduces the growth of tumor cells in a subcutaneous model of tumor progression and increases survival in an orthotopic xenograft model. Dietary-mediated anticancer effects correlate with the reduction of mTOR effector expression.</p><p><b>Conclusions:</b> We demonstrate that the sHFLC diet is a viable treatment alternative to the KD, and should be considered for clinical testing. <i>Clin Cancer Res; 22(10); 2482–95. ©2015 AACR</i>.</p></div>
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
