Anaplerosis in cancer Another step beyond the warburg effect英文文献资料.docVIP

American Journal of Molecular Biology, 2012, 2, 291-303 AJMB /10.4236/ajmb.2012.24031 Published Online October 2012 (http://www.SciRP.org/journal/ajmb/) Anaplerosis in cancer: Another step beyond the Warburg effect Estefania Ochoa-Ruiz , Rodrigo Diaz-Ruiz 1 2 1 Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico Facultad de Medicina, Programa de Posgrado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma 2 de México, Mexico City, Mexico Email: rdruiz8@ Received 28 July 2012; revised 1 September 2012; accepted 10 September 2012 ABSTRACT formation of malignant tumors, which in some cases can spread out to distant sites in the body (metastasis). Dur- ing the last decades, the research on cancer has intensi- fied and some important discoveries have been made in the field, such as the identification of oncogenes, tumor suppressor genes and the development of targeted anti- tumor drugs. In spite of these advances and some para- digm-shifting breakthroughs, the clinical progress is minimal and it is possible that additional and more spe- cific therapeutic targets remain to be discovered. Still, one of the main challenges for cancer therapy is to dis- criminate between malignant and normal cells. Biosynthesis is up-regulated in tumors and thus the demand for anabolic intermediates is increased. The metabolic routes providing the building blocks for macromolecules are thus a very attractive target as they are not normally up-regulated in a normal qui- escent cell. Some routes for glycolysis-derived inter- mediates production have been identified, but these do not constitute the whole pool of biosynthetic mole- cules in the cell, as many of these derive from mito- chondria in the Krebs cycle. Indeed, this metabol