Multidrug-resistant phenotype in retinoblastoma correlates with P-glycoprotein expression.
Chemotherapy plays an important role in therapy for patients with extraocular and metastatic retinoblastoma. The authors used chemotherapy for management of selected patients with uncontrolled intraocular tumors or tumors larger and more posteriorly located than those conventionally treated with local cryotherapy or photocoagulation. Rapid regrowth of some tumors after an initial excellent chemotherapy response led us to investigate the hypothesis that failure of treatment is caused by P-glycoprotein-related multidrug resistance. By using a sensitive immunoperoxidase method, increased P-glycoprotein was detected in five multidrug-resistant and two selectively plant alkaloid-resistant retinoblastoma cell lines and in the intraocular and metastatic tumors from which they were derived. In four chemotherapy-treated cases, increased P-glycoprotein in the tumor samples correlated with clinically relevant drug resistance. None of the four chemosensitive tumor cell lines had increased P-glycoprotein expression. Continuous surveillance of P-glycoprotein levels in metastatic retinoblastoma may be a useful guide to drug therapy.
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
H S
HS
Chan
P S
PS
Thorner
G
G
Haddad
B L
BL
Gallie
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005134:Eye Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001798:Blood Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins