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View the Table of Contents for the December 2007 issue of Molecular Cancer Therapeutics
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TRAIL, a TNF superfamily member, targets death receptors and selectively kills malignant cells while leaving normal cells unaffected. However, unlike most cancers, many osteosarcomas are resistant to TRAIL. Locklin and colleagues investigated this resistance using TRAIL and agonist antibodies to the death receptors DR4 and DR5 and found that MG-63 osteosarcoma cells carry a dominant-negative mutation which can confer TRAIL resistance. However an agonist antibody to the active death receptor was able to induce apoptosis in these resistant cells. Thus treatment with an appropriate receptor agonist can override cellular defences and could provide a tailored approach to treat resistant osteosarcomas.
Shukla et al. Page 3279 The multidrug resistance-linked ABCG2 transporter plays an important role in the body by acting as a barrier to limit the oral bioavailability of the drugs and also protects cells by transporting toxic compounds out of the cells. Shukla and colleagues found that the naphthoquinones, vitamin K3 (also called menadione) and its structural analog plumbagin are substrates of this transporter and these compounds at low micromolar concentrations inhibit the ABCG2-mediated efflux of anticancer substrates. This study identified menadione as a physiological substrate of ABCG2 and further suggests potential use of menadione and its analogs to increase the efficacy of chemotherapy in cancer patients.
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