Warburg, update

Warburg effect:

 As described by Warburg more than 50 years ago, tumour cells maintain a high glycolytic rate even in conditions of adequate oxygen supply. However, most of tumours are subjected to hypoxic conditions due to the abnormal vasculature that supply them with oxygen and nutrients. Thus, glycolysis is essential for tumour survival and spread. A key step in controlling glycolytic rate is the conversion of fructose-6-P to fructose-1,6-P(2) by 6-phosphofructo-1-kinase (PFK-1). The activity of PFK-1 is allosterically controlled by fructose-2,6-P(2), the product of the enzymatic activity of a dual kinase/phosphatase family of enzymes (PFKFB1-4) that are increased in a significant number of tumour types.. Thus, targeting PFKFB enzymes, either directly or through inhibition of HIF-1, appears as a promising approach for the treatment of certain tumours. In turn, these enzymes are induced by hypoxia through the activation of the HIF-1 complex (hypoxia-inducible complex-1), a transcriptional activator that controls the expression of most of hypoxia-regulated genes. HIF-1 complex is overexpressed in a variety of tumours and its expression appears to correlate with poor prognosis and responses to chemo or radiotherapy
 PMID: 17661163 [PubMed – indexed for MEDLINE

Cancer and Copper



 Laboratory Study Explains Clinical Promise Of Anti-Angiogenesis Cancer Drug
 Copper-Lowering Drug Stabilizes Advanced Cancer In Anti-angiogenesis Trial Cancer Cells Forming Blood Vessels Send Their Copper To The Edge


 X-ray fluorescence microscopy reveals large-scale relocalization and extracell    (edited by Judah Folkman)
 Copper Control as an Antiangiogenic Anticancer Therapy: Lessons from Treating Tetrathiomolybdate Inhibits Angiogenesis and Metastasis Through Suppression of Tetrathiomolybdate promotes tumor necrosis and pr events distant metastases by
 Copper-dependent activation of hypoxia-inducible f…[Blood. 2005] – PubMed Re