Abstract
Neural crest tumors of childhood are particularly resistant to apoptosis induction by chemotherapeutic agents. Mechanisms of resistance include altered glutathione handling that accompanies up-regulation of Bcl-2 and its relatives. We have designed and tested in preclinical model systems approaches to this problem. These approaches include adjunctive use of oxygen radical-generating neurotransmitter analogs taken up by these neural crest tumor cells with scavenging (i.e., “rescue”) agents that are selective for normal neural crest and the use of reduction-dependent prodrugs of apoptosis-inducing agents. Promising prototypes for these conceptual approaches include, respectively, adjunctive use of the oxygen radical generator, 6-hydroxydopamine, with the normal cell-selective antioxidant, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), and use of the reduction-dependent chemotherapeutic prodrug neocarzinostatin.
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Schor, N.F., Kagan, V.E., Liang, Y. et al. Exploiting Oxidative Stress and Signaling in Chemotherapy of Resistant Neoplasms. Biochemistry (Moscow) 69, 38–44 (2004). https://doi.org/10.1023/B:BIRY.0000016349.75384.e6
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DOI: https://doi.org/10.1023/B:BIRY.0000016349.75384.e6