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Retinoid therapy of high-risk neuroblastoma.

Abstract：

:Retinoids are derivatives of vitamin A that include all trans-retinoic acid (ATRA), 13-cis-retinoic acid, (13-cis-RA), and fenretinide (4-HPR). High levels of either ATRA or 13-cis-RA can cause arrest of cell growth and morphological differentiation of human neuroblastoma cell lines, and phase I trials showed that higher and more sustained drug levels were obtained with 13-cis-RA relative to ATRA. A phase III randomized trial showed that high-dose, pulse therapy with 13-cis-RA given after completion of intensive chemoradiotherapy (with or without autologous bone marrow transplantation) significantly improved event-free survival in high-risk neuroblastoma. The cytotoxic retinoid 4-HPR achieved multi-log cell kills in neuroblastoma cell lines resistant to ATRA and 13-cis-RA, and a pediatric phase I trial has shown it to be well tolerated. Cytotoxicity of 4-HPR is mediated at least in part by increasing tumor cell ceramide levels and combining 4-HPR with ceramide modulators increased anti-tumor activity in pre-clinical models. Thus, further clinical trials of 4-HPR in neuroblastoma, and of 4-HPR in combination with ceramide modulators, are warranted.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Reynolds CP,Matthay KK,Villablanca JG,Maurer BJ

doi

10.1016/s0304-3835(03)00108-3

keywords:

subject

Has Abstract

pub_date

2003-07-18 00:00:00

pages

185-92

issue

1-2

eissn

0304-3835

issn

1872-7980

pii

S0304383503001083

journal_volume

197

pub_type

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