Impairments in antifolate transport are common in retinoblastoma tumor samples. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Many patients with retinoblastoma have a genetic predisposition to cancer and external beam radiation therapy and alkylating agent chemotherapy may increase their risk of secondary malignancy. Identification of effective chemotherapy agents for retinoblastoma that are not associated with an elevated risk of secondary malignancy would be beneficial. PROCEDURE: Twenty-six specimens of fresh retinoblastoma tumor cells were studied in vitro with a PT430 competitive displacement assay. Differential displacement of the PT430 by methotrexate and not trimetrexate was considered indicative of a defect in reduced folate carrier (RFC)-mediated transport. Elevations in the accumulation of PT430 were considered indicative of dihydrofolate reductase (DHFR) amplification. RESULTS: In 9 of the 26 (35%) samples, displacement by methotrexate was less than half the displacement by trimetrexate indicative of a defect in the RFC. In 5 of the 26 (19%) samples, trimetrexate did not displace the PT430. In 7 of 26 (27%) samples, the peak PT430 accumulation was suggestive of DHFR overexpression. Overall 9 of 26 (35%) samples had no evidence of a transport defect or DHFR overexpression and would be anticipated to be potentially sensitive to methotrexate. In 15 of the 26 (58%), no defects existed in trimetrexate displacement or DHFR overexpression and would be anticipated to be potentially sensitive to trimetrexate. CONCLUSION: These results would support consideration of a phase II study to determine the effectiveness of trimetrexate for recurrent intra-ocular retinoblastoma.

publication date

  • March 1, 2008

Research

keywords

  • Antimetabolites, Antineoplastic
  • Folic Acid Antagonists
  • Membrane Transport Proteins
  • Methotrexate
  • Neoplasm Proteins
  • Retinal Neoplasms
  • Retinoblastoma
  • Tetrahydrofolate Dehydrogenase
  • Trimetrexate

Identity

Scopus Document Identifier

  • 38549084679

Digital Object Identifier (DOI)

  • 10.1002/pbc.21266

PubMed ID

  • 17554792

Additional Document Info

volume

  • 50

issue

  • 3