Anthracycline drug targeting

Cytoplasmic versus nuclear - A fork in the road

Leonard Lothstein, Mervyn Israel, Trevor W. Sweatman

Research output: Contribution to journalReview article

58 Citations (Scopus)

Abstract

The anthracycline antibiotics doxorubicin (Adriamycin; DOX) and daunorubicin (DNR) continue to be essential components of first-line chemotherapy in the treatment of a variety of solid and hematopoietic tumors. The overall efficacies of DOX and DNR are, however, impeded by serious dose-limiting toxicities, including cardiotoxicity, and the selection of multiple mechanisms of cellular drug resistance. These limitations have necessitated the development of newer anthracyclines whose structural and functional modifications circumvent these impediments. In this review, we will present recent strategies in anthracycline design and assess their potential therapeutic merits. Current anthracycline design has diverged to target either cytoplasmic or nuclear sites. Nuclear targets have been broadened to include not only topoisomerase II (topo II) inhibition through ternary complex stabilization and catalytic inhibition, but also topoisomerase I (topo I) inhibition and transcriptional inhibition. In contrast, cytoplasmic targeting focuses on anthracycline binding to protein kinase C (PKC) regulatory domain with consequent modulation of activity.

Original languageEnglish (US)
Pages (from-to)169-177
Number of pages9
JournalDrug Resistance Updates
Volume4
Issue number3
DOIs
StatePublished - Jan 1 2001

Fingerprint

Anthracyclines
Drug Delivery Systems
Daunorubicin
Doxorubicin
Type II DNA Topoisomerase
Type I DNA Topoisomerase
Drug Resistance
Protein Kinase C
Carrier Proteins
Anti-Bacterial Agents
Drug Therapy
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Cancer Research
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Anthracycline drug targeting : Cytoplasmic versus nuclear - A fork in the road. / Lothstein, Leonard; Israel, Mervyn; Sweatman, Trevor W.

In: Drug Resistance Updates, Vol. 4, No. 3, 01.01.2001, p. 169-177.

Research output: Contribution to journalReview article

Lothstein, Leonard ; Israel, Mervyn ; Sweatman, Trevor W. / Anthracycline drug targeting : Cytoplasmic versus nuclear - A fork in the road. In: Drug Resistance Updates. 2001 ; Vol. 4, No. 3. pp. 169-177.
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