Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks
- 12 April 2004
- journal article
- review article
- Published by Springer Nature in Oncogene
- Vol. 23 (16) , 2934-2949
Abstract
Intrinsic (innate) and acquired (adaptive) resistance to chemotherapy critically limits the outcome of cancer treatments. For many years, it was assumed that the interaction of a drug with its molecular target would yield a lethal lesion, and that determinants of intrinsic drug resistance should therefore be sought either at the target level (quantitative changes or/and mutations) or upstream of this interaction, in drug metabolism or drug transport mechanisms. It is now apparent that independent of the factors above, cellular responses to a molecular lesion can determine the outcome of therapy. This review will focus on programmed cell death (apoptosis) and on survival pathways (Bcl-2, Apaf-1, AKT, NF-B) involved in multidrug resistance. We will present our molecular interaction mapping conventions to summarize the AKT and IB/NF-B networks. They complement the p53, Chk2 and c-Abl maps published recently. We will also introduce the 'permissive apoptosis-resistance' model for the selection of multidrug-resistant cells.Keywords
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