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lundi 11 février 2013

Cancer and the carbohydrate restriction diet

The Warburg hypothesis is not a magic bullet against cancer. However high CH diets are proinflammatory diets and bring a very useful fuel to cancer cells. Time is come to go on clinical trials with CR diet in cancer patients.

The biochemistry

The IGF1R-IR/PI3K/Akt/mTOR pathway and its manipulation through diet. Elevations in blood glucose concentrations lead to secretion of insulin with subsequent elevation of free IGF1. Binding of insulin and IGF1 to their receptor tyrosine kinases induces autophosphorylation of the latter which leads to subsequent activation of PI3K by one of at least three different pathways [54]. Further downstream, PI3K signaling causes phosphorylation and activation of the serine/threonine kinase Akt (also known as protein kinase B). Akt activates mammalian target of rapamycin (mTOR), which itself induces aerobic glycolysis by up-regulating key glycolytic enzymes, in particular via its downstream effectors c-Myc and hypoxia inducible factor (HIF)-1α. mTOR is negatively affected through activation of AMPK, which can be achieved by dietary restriction [67]. In addition, a possible negative interaction between insulin and AMPK is discussed in vivo [60].

The pathways

Development of the cachectic state via sustained inflammatory signaling. Glucose metabolism in peripheral tissues is impaired already at early stages, while hepatic gluconeogenesis increases during tumor progression at later stages.




Nutrient Restriction and Radiation Therapy for Cancer Treatment: When Less Is More

  1. Nicole L. Simonea
+ Author Affiliations
  1. aDepartment of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA;
  2. bDepartment of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  1. Correspondence: Nicole Simone, M.D., Department of Radiation Oncology, Thomas Jefferson University, Kimmel Cancer Center, Bodine Center for Cancer Treatment, 111 S. 11th Street, G-301G, Philadelphia, Pennsylvania 19107, USA. Telephone: 215-503-0554; Fax: 215-955-0412; e-mail:
  • Received April 11, 2012.
  • Accepted September 24, 2012.
  • First published online in THE ONCOLOGIST Express on January 8, 2013.

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