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. 2009 Feb;5(1):239-45.
doi: 10.2147/tcrm.s4749. Epub 2009 Mar 26.

Challenging issues in molecular-targeted therapy

Zoheir Ezziane  1
Affiliations

Challenging issues in molecular-targeted therapy

Zoheir Ezziane. Ther Clin Risk Manag. 2009 Feb.

Abstract

There are variety of anticancer treatments including chemotherapeutic drugs, which are known to induce cell growth arrest and apoptosis through DNA damage and cytoskeleton toxicity. Meanwhile, histone deacetylase (HDAC) inhibitors could apply their antitumor activity through chromatin remodeling and gene expression modulation that affect the cell cycle and survival pathways. This paper proposes an anticancer three-drug compound and discusses several challenging issues in relation to designing multidrug compounds that could possibly lead to molecular-targeted therapies.

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Figures

Figure 1
Figure 1
Representation of concomitant molecular changes after combination treatment with a potential compound: Combination therapies with agents that target endothelial cells to block angiogenesis, EGFR/ERBB2, and histone deacetylase inhibitors to prevent tumor adaptation in cancer treatment warrants experimental studies. Abbreviations: EGFR, epidermal growth factor receptor; ErbB2, epidermal receptor growth factor 2; VEGF, vascular endothelial growth factor.
Figure 2
Figure 2
Complex receptor-ligand: Delta-Ex3 (a Survivin isoform) and XY2 (an HRas ligand). This complex has been properly visualized using CheVi (R) (a Linux-based Chemical Visualizer), where XY2 ligand is shown docked along Delta-Ex3’s surface and deeply embedded in a particular active site.
Figure 3
Figure 3
Design of the proposed three-drug combination experiment. Abbreviations: EGFR, epidermal growth factor receptor; ErbB2, epidermal receptor growth factor 2; HDAC, histone deacetylase; INH, inhibitor; VEGF, vascular endothelial growth factor.
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