Personalized Cancer Medicine: From Molecular Diagnostics to Targeted Therapy with Natural Products

 

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Abstract

Personalized cancer medicine aims to develop individualized treatment options adapted to factors relevant for the prognosis of each patient. Molecular biomarkers are required to predict the likelihood of an individual tumor's responsiveness or of toxicity in normal organs and to advise optimized treatments with improved efficacy at reduced side effects for each cancer patient. In the present review, we present a concept, which takes advantage of methods of molecular diagnostics to identify predictive markers at the DNA, mRNA, and protein levels. Markers with prognostic value concerning treatment response and patient survival can then be used as targets to develop optimized drugs. We focus on three examples to illustrate this strategy: (i) chemoselective treatment of tumors with 9p21 deletion by L-alanosine, (ii) treatment of multidrug-resistant P-glycoprotein-expressing tumor cells by non-cross-resistant natural products or by inhibitors of P-glycoprotein to overcome multidrug resistance, and (iii) natural products that inhibit the epidermal growth factor receptor (EGFR) in EGFR-overexpressing tumor cells.

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• 125 Efferth T, Konkimalla V B, Wang Y F, Sauerbrey A, Meinhardt S, Zintl F, Mattern J, Volm M. Prediction of broad spectrum resistance of tumors towards anti-cancer drugs.  Clin Cancer Res. 2008;  14 2405-2412
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• 129 Adams M, Mahringer A, Kunert O, Fricker G, Efferth T, Bauer R. Cytotoxicity and p-glycoprotein modulating effects of quinolones and indoloquinazolines from the Chinese herb Evodia rutaecarpa.  Planta Med. 2007;  73 1554-1557
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• 131 Majumder S, Dutta P, Mukherjee P, Datta E R, Efferth T, Bhattacharya S, Choudhuri S K. Reversal of drug resistance in P-glycoprotein-expressing T-cell acute lymphoblastic CEM leukemia cells by copper N-(2-hydroxy acetophenone) glycinate and oxalyl bis(N-phenyl)hydroxamic acid.  Cancer Lett. 2006;  244 16-23
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• 132 Mookerjee A, Basu J M, Majumder S, Chatterjee S, Panda G S, Dutta P, Pal S, Mukherjee P, Efferth T, Roy S, Choudhuri S K. A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo.  BMC Cancer. 2006;  6 267
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• 135 Perea S, Hidalgo M. Predictors of sensitivity and resistance to epidermal growth factor receptor inhibitors.  Clin Lung Cancer. 2004;  6 S30-S34
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• 147 Volm M, Efferth T, Mattern J. Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p 53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations.  Anticancer Res. 1992;  12 11-20
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Thomas Efferth

Department of Pharmaceutical Biology
Institute of Pharmacy and Biochemistry
University of Mainz

Staudinger Weg 5

55128 Mainz

Germany

Phone: + 49 6 13 13 92 57 51

Fax: + 49 6 13 13 92 37 52

Email: efferth@uni-mainz.de