Multidrug resistance protein (MRP) expression in retinoblastoma correlates with the rare failure of chemotherapy despite cyclosporine for reversal of P-glycoprotein

• Published in: Cancer research (Chicago, Ill.) Vol. 57; no. 12; pp. 2325 - 2330
• Main Authors: CHAN, H. S. L, LU, Y, GROGAN, T. M, HADDAD, G, HIPFNER, D. R, COLE, S. P. C, DEELEY, R. G, LING, V, GALLIE, B. L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.06.1997
• Subjects: Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATP-Binding Cassette Transporters - metabolism; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Biological and medical sciences; Chemotherapy; Child, Preschool; Combined Modality Therapy; Cyclosporine - administration & dosage; Drug Resistance, Neoplasm; Eye Enucleation; Eye Neoplasms - metabolism; Eye Neoplasms - therapy; Humans; Immunohistochemistry; Infant; Infant, Newborn; Medical sciences; Multidrug Resistance-Associated Proteins; Neoplasm Proteins - metabolism; Pharmacology. Drug treatments; Retinoblastoma - metabolism; Retinoblastoma - therapy; Human; Antineoplastic agent; Nervous system diseases; Drug combination; Retinopathy; Intraocular; Malignant tumor; Recurrent; Eye disease; Chemotherapy; Multiple resistance; Ciclosporin; Mechanism of action; Retinoblastoma; Child
• ISSN: 0008-5472; 1538-7445

Failure of chemotherapy associated with expression of the multidrug resistance protein p170 frequently occurs in retinoblastoma (RB). Despite using cyclosporine, which inhibits p170 and improves our chemotherapy results, rare failures occur. In nonmetastatic primarily enucleated RBs, we show expression of p170 in 3 of 18 samples and expression of multidrug resistance protein (MRP), the second protein associated with resistance to chemotherapy, in 1 of 18 samples. All three RBs that failed chemotherapy without cyclosporine expressed MRP with p170. All three RBs that were enucleated immediately when chemotherapy failed despite the addition of cyclosporine expressed only MRP. One RB enucleated 2 years after failing chemotherapy with cyclosporine, despite radiation and salvage chemotherapy, expressed both p170 and MRP. Two metastatic RBs that expressed both p170 and MRP at diagnosis and at recurrence failed chemotherapy without cyclosporine, whereas one metastatic RB that expressed neither protein was cured by chemotherapy without cyclosporine. MRP may result in failure of chemotherapy despite the elimination of p170-expressing clones by cyclosporine.