Sphingolipids in neuroblastoma: their role in drug resistance mechanisms.

Abstract

Disseminated neuroblastoma usually calls for chemotherapy as the primary approach for treatment. Treatment failure is often attributable to drug resistance. This involves a variety of cellular mechanisms, including increased drug efflux through expression of ATP-binding cassette transporters (e.g., P-glycoprotein) and the inability of tumor cells to activate or propagate the apoptotic response. In recent years it has become apparent that sphingolipid metabolism and the generation of sphingolipid species, such as ceramide, also play a role in drug resistance. This may involve an autonomous mechanism, related to direct effects of sphingolipids on the apoptotic response, but also a subtle interplay between sphingolipids and ATP-binding cassette transporters. Here, we present an overview of the current understanding of the multiple levels at which sphingolipids function in drug resistance, with an emphasis on sphingolipid function in neuroblastoma and how modulation of sphingolipid metabolism may be used as a novel treatment paradigm.

• Authors: Hannie Sietsma, Anne Jan Dijkhuis, Willem Kamps, Jan Willem Kok
• Journal: Neurochemical research (Neurochem Res) Vol. 27 Issue 7-8 Pg. 665-74 (Aug 2002) ISSN: 0364-3190 [Print] United States
• PMID: 12374201 (Publication Type: Journal Article, Review)

Chemical References

• Sphingolipids

Topics

• Animals
• Drug Resistance, Multiple (physiology)
• Drug Resistance, Neoplasm (physiology)
• Humans
• Neuroblastoma (pathology, physiopathology)
• Sphingolipids (physiology)