Role of apoptosis and apoptosis-related genes in cellular response and antitumor efficacy of anthracyclines

Paola Perego, Elisabetta Corna, Michelandrea De Cesare, Laura Gatti, Donatella Polizzi, Graziella Pratesi, Rosanna Supino, Franco Zunino

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 doxurubicin, 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 apoptosis-related 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.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalCurrent Medicinal Chemistry
Volume8
Issue number1
Publication statusPublished - 2001

Fingerprint

Anthracyclines
Genes
Apoptosis
Tumors
Drug Resistance
Pharmaceutical Preparations
DNA Damage
Neoplasms
Disaccharides
DNA
Cell death
Cytotoxicity
Drug Interactions
Doxorubicin
Cell Death
Cells

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Role of apoptosis and apoptosis-related genes in cellular response and antitumor efficacy of anthracyclines. / Perego, Paola; Corna, Elisabetta; De Cesare, Michelandrea; Gatti, Laura; Polizzi, Donatella; Pratesi, Graziella; Supino, Rosanna; Zunino, Franco.

In: Current Medicinal Chemistry, Vol. 8, No. 1, 2001, p. 31-37.

Research output: Contribution to journalArticle

Perego, P, Corna, E, De Cesare, M, Gatti, L, Polizzi, D, Pratesi, G, Supino, R & Zunino, F 2001, 'Role of apoptosis and apoptosis-related genes in cellular response and antitumor efficacy of anthracyclines', Current Medicinal Chemistry, vol. 8, no. 1, pp. 31-37.
Perego, Paola ; Corna, Elisabetta ; De Cesare, Michelandrea ; Gatti, Laura ; Polizzi, Donatella ; Pratesi, Graziella ; Supino, Rosanna ; Zunino, Franco. / Role of apoptosis and apoptosis-related genes in cellular response and antitumor efficacy of anthracyclines. In: Current Medicinal Chemistry. 2001 ; Vol. 8, No. 1. pp. 31-37.
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