Abstract
Cellular resistance to anthracyclines is a major limitation of their clinical use in the treatment of human tumors. Resistance to doxorubicin is described as a multifactorial phenomenon involving the overexpression of defense factors and alterations in drug-target interactions. Such changes do not account for all manifestations of drug resistance, in particular intrinsic resistance of solid tumors. Since anthracyclines can induce apoptotic cell death, an alternative promising approach to drug resistance has focused on the study of cellular response to drug-induced DNA damage, with particular reference to the relationship between cytotoxicity/antitumor efficacy and apoptotic response. The evidence that a novel disaccharide analog (MEN 10755), endowed with an improved preclinical activity over doxorubicin, was also more effective as an inducer of apoptosis provided additional insights to better understand the cellular processes that confer sensitivity to anthracyclines. Although the presence or alteration of a single apoptosisrelated factor (e.g., p53, bcl-2) is not predictive of the sensitivity/resistance status, the complex interplay among DNA damage-activated pathways is likely an important determinant of tumor cell sensitivity to anthracyclines.
Current Medicinal Chemistry
Title: Role of Apoptosis and Apoptosis-Related Genes in Cellular Response and Antitumor Efficacy of Anthracyclines
Volume: 8 Issue: 1
Author(s): Paola Perego, Elisabetta Corna, Michelandrea De Cesare, Laura Gatti, Donatella Polizzi, Graziella Pratesi, Rosanna Supino and Franco Zunino
Affiliation:
Abstract: Cellular resistance to anthracyclines is a major limitation of their clinical use in the treatment of human tumors. Resistance to doxorubicin is described as a multifactorial phenomenon involving the overexpression of defense factors and alterations in drug-target interactions. Such changes do not account for all manifestations of drug resistance, in particular intrinsic resistance of solid tumors. Since anthracyclines can induce apoptotic cell death, an alternative promising approach to drug resistance has focused on the study of cellular response to drug-induced DNA damage, with particular reference to the relationship between cytotoxicity/antitumor efficacy and apoptotic response. The evidence that a novel disaccharide analog (MEN 10755), endowed with an improved preclinical activity over doxorubicin, was also more effective as an inducer of apoptosis provided additional insights to better understand the cellular processes that confer sensitivity to anthracyclines. Although the presence or alteration of a single apoptosisrelated factor (e.g., p53, bcl-2) is not predictive of the sensitivity/resistance status, the complex interplay among DNA damage-activated pathways is likely an important determinant of tumor cell sensitivity to anthracyclines.
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Perego Paola, Corna Elisabetta, De Cesare Michelandrea, Gatti Laura, Polizzi Donatella, Pratesi Graziella, Supino Rosanna and Zunino Franco, Role of Apoptosis and Apoptosis-Related Genes in Cellular Response and Antitumor Efficacy of Anthracyclines, Current Medicinal Chemistry 2001; 8 (1) . https://dx.doi.org/10.2174/0929867013373994
DOI https://dx.doi.org/10.2174/0929867013373994 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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