Role of Chemotherapy Resistance Genes in Outcome of Neuroblastoma

Pediatr Blood Cancer. 2007 Mar;48(3):311-7. doi: 10.1002/pbc.20853.

Abstract

Background: Neuroblastoma is a heterogeneous pediatric disease. Most patients with localized disease usually have a favorable prognosis, but patients with advanced disease have a poor prognosis despite combination chemotherapy. Treatment failure may be attributable to resistance to cytotoxic drugs.

Procedure: Using quantitative RT-PCR, we investigated the clinical significance of the level of mRNA expression of multidrug resistance genes (MDR1, MRP1, MRP5, LRP) in a series of 29 advanced neuroblastoma samples.

Results: At the end of induction chemotherapy, 48% of patients achieved a clinical complete response, 28% achieved a partial response or stable disease, and 24% presented progressive disease. MDR1 mRNA overexpression (i.e., mRNA level >2 copies of MDR1 gene) was observed in 74% of samples, and MRP1, MRP5, LRP overexpression was observed less frequently (30, 33, and 33% of samples, respectively). None of these parameters were predictive of response, relapse, or survival. However, clinical response to treatment was highly predictive of relapse-free survival and overall survival.

Conclusions: High expression of these multidrug resistance genes in advanced neuroblastoma is not the main parameter of response to cytotoxic drugs; clinical response to treatment remains the most important parameter in predicting the prognosis of patients with advanced neuroblastoma, until other relevant laboratory parameters have been identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human, Pair 1 / ultrastructure
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology
  • Computer Systems
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Etoposide / administration & dosage
  • Etoposide / pharmacology
  • Female
  • Gene Expression Profiling
  • Genes, MDR*
  • Genes, myc
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Multidrug Resistance-Associated Proteins / biosynthesis
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / physiology
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neuroblastoma / drug therapy
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Neuroblastoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • S Phase
  • Treatment Outcome
  • Vault Ribonucleoprotein Particles / biosynthesis
  • Vault Ribonucleoprotein Particles / genetics
  • Vault Ribonucleoprotein Particles / physiology
  • Vincristine / administration & dosage
  • Vincristine / pharmacology

Substances

  • ABCC5 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Carboplatin
  • Cisplatin
  • multidrug resistance-associated protein 1