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

Thomas Efferth

doi:10.1055/s-0030-1249937

Planta Medica, Inhaltsverzeichnis

Planta Med 2010; 76(11): 1143-1154
DOI: 10.1055/s-0030-1249937

Cancer Therapy

Reviews
© Georg Thieme Verlag KG Stuttgart · New York

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

Thomas Efferth¹

¹Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany

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.

Key words

chemotherapy - comparative genomic hybridization - drug resistance - pharmacogenomics - pharmacognosy - traditional Chinese medicine

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Referenzen

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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
133 Mookerjee A, Mookerjee Basu J, Dutta P, Majumder S, Bhattacharyya S, Biswas J, Pal S, Mukherjee P, Raha S, Baral R N, Das T, Efferth T, Sa G, Roy S, Choudhuri S K. Overcoming drug-resistant cancer by a newly developed copper chelate through host-protective cytokine-mediated apoptosis. Clin Cancer Res. 2006; 12 4339-4349
134 Weiss J, Rose J, Storch C H, Ketabi-Kiyanvash N, Sauer A, Haefeli W E, Efferth T. Modulation of human BCRP (ABCG2) activity by anti-HIV drugs. J Antimicrob Chemother. 2007; 59 238-245
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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142 Seigneuric R, Starmans M H, Fung G, Krishnapuram B, Nuyten D S, van Erk A, Magagnin M G, Rouschop K M, Krishnan S, Rao R B, Evelo C T, Begg A C, Wouters B G, Lambin P. Impact of supervised gene signatures of early hypoxia on patient survival. Radiother Oncol. 2007; 83 374-382
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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

Thomas Efferth

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

Staudinger Weg 5

55128 Mainz

Germany

Telefon: + 49 6 13 13 92 57 51

Fax: + 49 6 13 13 92 37 52

eMail: efferth@uni-mainz.de