Inpharma 1257 - 30 Sep 2000

Flavopiridol + oligonucleotides:synergistic antitumour activity

Combined administration of flavopiridol and anantisense oligonucleotide which inhibits the expressionof the cyclin-dependent kinase inhibitor p27Kip-1 resultsin synergistic antitumour activity, report researchersfrom Germany.

In this study, athymic nude mice bearing humanprostate cancer cells received 4 cycles of flavopiridolalone, antisense oligonucleotide alone, a scrambledoligonucleotide alone, a combination of flavopiridol withantisense or scrambled oligonucleotide, or remaineduntreated.

‘Strongly synergistic’Monotherapy with either of the oligonucleotides had

little effect on tumour growth; importantly, antisenseoligonucleotide did not enhance tumour growth.Administration of flavopiridol, either alone or withscrambled oligonucleotide, resulted in modestinhibition of tumour growth. In contrast, thecombination of flavopiridol with antisenseoligonucleotide ‘was strongly synergistic and led to adramatic retardation of tumor growth’, say theresearchers.

Histological examination of tumours showeddisintegration of tumour tissue in flavopiridol recipients,with this effect being greater in tumours exposed toflavopiridol in combination with antisenseoligonucleotides. The researchers note that tumoursfrom recipients of flavopiridol plus antisenseoligonucleotides ‘contained appreciable numbers ofapoptotic cells’.Achenbach TV, et al. Synergistic antitumor effect of chemotherapy and antisense-mediated ablation of the cell cycle inhibitor p27(KIP-1). Clinical cancer research:an official journal of the American Association for Cancer Research 6: 3006-3014,Aug 2000 800844405

» Editorial comment: Flavopiridol is in phase II trials forlymphoma and multiple myeloma in the US with Aventis.Flavopiridol is also in phase II trials for renal cancer and solidtumours.

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Inpharma 30 Sep 2000 No. 12571173-8324/10/1257-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved