Use of Metabolic Pathway Flux Information in Anticancer Drug Design

Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2007/4)


The metabolic phenotype of tumor cells promote the proliferative state, which indicates that (a) cell transformation is associated with the activation of specific metabolic substrate channels toward nucleic acid synthesis and (b) increased expression phosphorylation, allosteric or transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate unlimited growth. It is evident that cell transformation due to various K-ras point mutations is associated with the activation of specific metabolic substrate channels that increase glucose channeling toward nucleic acid synthesis. Therefore, phosphorylation, allosteric and transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate cell transformation and growth. In this review, we summarize opposite changes in metabolic phenotypes induced by various cell-transforming agents, and tumor growth-inhibiting drugs or phytochemicals, or novel synthetic antileukemic drugs such as imatinib mesylate (Gleevec). Metabolic enzymes that further incite growth signaling pathways and thus promote malignant cell transformation serve as high-efficacy nongenetic novel targets for cancer therapies.


Metabolic Phenotype Pyruvate Carboxylase Nucleic Acid Synthesis Glucose Carbon Increase Glucose Utilization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was, in part, supported by the PHS M01-RR00425 of the General Clinical Research Unit, by NIH-AT00151, by P01-CA42710 of the UCLA Clinical Nutrition Research Unit Stable Isotope Core, its 009826-00-00 Preliminary Feasibility grant to LGB and by P01 AT003960-01 UCLA Center for Excellence in Pancreatic Diseases, Metabolomics Core, and a grant from the Hirshberg Foundation for Pancreatic Cancer Research.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.Harbour-UCLA Medical Center RB1Los Angeles Biomedical Research InstituteTorranceUSA

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