Utility of Antioncogene Ribozymes and Antisense Oligonucleotides in Reversing Drug Resistance

The development of new anticancer drugs and the identification of novel targets are a major focus for pharmaceutical and biotech companies, universities, and research institutes worldwide (1 ). However, the therapeutic efficacy of anticancer drugs against malignant diseases is limited because of the selection and regrowth of drug-resistant cells. The development of approaches to overcome and/or circumvent drug resistance will depend on a precise understanding of the mechanisms of resistance not only at the target tumor cell level but also in vivo. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and genetic differences in somatic cells in tumors. We have focused on two anticancer drugs: cisplatin, which is exceptionally effective against testicular cancer, ovarian cancer, and others (2 ); and Ara-C (1-β-d -arabinofuranosyl cytidine, cytosine arabinoside), now a standard for the treatment of acute and chronic leukemia (3 ).