title: Role of apoptosis and apoptosis-related genes in cellular response and antitumor efficacy of anthracyclines.
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 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
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian1, 20133 Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Perego
authors.forename: E
authors.initials: E
authors.lastname: Corna
authors.forename: M
authors.initials: M
authors.lastname: De Cesare
authors.forename: L
authors.initials: L
authors.lastname: Gatti
authors.forename: D
authors.initials: D
authors.lastname: Polizzi
authors.forename: G
authors.initials: G
authors.lastname: Pratesi
authors.forename: R
authors.initials: R
authors.lastname: Supino
authors.forename: F
authors.initials: F
authors.lastname: Zunino
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic