Major cytogenetic aberrations and typical multidrug resistance phenotype of uveal melanoma: current views and new therapeutic prospects.
Uveal melanoma is the most frequent intra-ocular cancer. The recent development of new chromosome-related technologies have permitted the elucidation of both the cytogenetics and the natural history of this disease. Fifty to 60% of uveal melanomas are linked to a monosomy 3, which appears as an early and determinant event in tumor progression. Tumors with this anomaly have a very poor prognosis. Recent work suggests that this category of uveal melanoma represents a distinct pathologic entity from that associated with normal disomy 3. Chromosome 6 aberrations probably constitute a second entry point into the process of cancerogenesis, while gains in 8q seem to appear later in the natural history of uveal melanomas due to their higher frequency in larger tumors. Other anomalies will be reviewed. In spite of significant improvements in the local treatment of uveal melanoma, many patients die due to tumor metastasis. This disease is characterized by a constitutive chemoresistance whose typical multidrug resistance phenotype (MDR) is particularly complex since different combinations of several resistance proteins are simultaneously produced. Regulation of the expression of these proteins is a research priority, increasingly so as gene therapy-dependent chemosensitization strategies expand. Therefore, the development and improvement of methods to determine the chemoresistance profile become a crucial objective today in the therapeutic strategies against uveal melanoma.
Baggetto
Loris G
LG
Institut de Biologie et Chimie des Protéines (IBCP UMR5086 CNRS UCBL), 7 Passage du Vercors, Lyon, France. lg.baggetto@ibcp.fr
Gambrelle
Joël
J
Dayan
Guila
G
Labialle
Stéphane
S
Barakat
Stéphane
S
Michaud
Mickaël
M
Grange
Jean-Daniel
JD
Gayet
Landry
L
D000970:Antineoplastic Agents / Q000494:pharmacology; D002869:Chromosome Aberrations / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D009006:Monosomy; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*
D000970:Antineoplastic Agents