MULTIDRUG-RESISTANCE IN LYMPHOMAS

被引:101
作者
YUEN, AR [1 ]
SIKIC, BI [1 ]
机构
[1] STANFORD UNIV,MED CTR,SCH MED,DEPT MED,DIV ONCOL,STANFORD,CA 94305
关键词
D O I
10.1200/JCO.1994.12.11.2453
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To discuss the significance of multidrug resistance (MDR) in human lymphomas and to review recent and ongoing clinical trials using MDR modulators. Design: A medical literature search was used to identify articles that reported results on the expression or modulation of MDR in human lymphomas. This review summarizes the various methods for detecting expression of the mdr1 gene in tumor specimens, the patterns of expression in lymphomas, and recent and upcoming clinical trials using modulating agents to reverse MDR. Results: There is considerable variation in the assays used to evaluate the expression of mdr1 in lymphomas. Current methodology includes reverse transcriptase polymerase chain reaction (rt-PCR) for assay of mdr1 mRNA, and immunohistochemistry or flow cytometry for detection of the multidrug transporter, p-glycoprotein (P-gp). The preponderance of evidence suggests that mdr1 expression is relatively low in untreated patients (10% to 20% of lymphomas positive), but increases in patients with recurrent disease (50% to 70% positive). Some evidence suggests that mdr1 expression is a prognostic factor for response to chemotherapy, as well as for subsequent survival. Verapamil and cyclosporine (CsA) have been used as competitive inhibitors of the multidrug transporter P-gp in early clinical trials. Although these studies show some activity in modulating clinical MDR, both verapamil and CsA manifest considerable toxicities at doses below those required for complete inhibition of P-gp function. Conclusion: MDR due to the expression of the mdr1 gene is an important factor in the course of patients with lymphomas. Continued clinical trials with more potent and less toxic modulators are needed to define the ultimate benefit of modulating MDR in lymphomas.
引用
收藏
页码:2453 / 2459
页数:7
相关论文
共 57 条
[1]   PHASE-I TRIAL OF DOXORUBICIN WITH CYCLOSPORINE AS A MODULATOR OF MULTIDRUG-RESISTANCE [J].
BARTLETT, NL ;
LUM, BL ;
FISHER, GA ;
BROPHY, NA ;
EHSAN, MN ;
HALSEY, J ;
SIKIC, BI .
JOURNAL OF CLINICAL ONCOLOGY, 1994, 12 (04) :835-842
[2]   MEMBRANE-MEDIATED DRUG-RESISTANCE AND PHENOTYPIC REVERSION TO NORMAL GROWTH-BEHAVIOR OF CHINESE-HAMSTER CELLS [J].
BIEDLER, JL ;
RIEHM, H ;
PETERSON, RHF ;
SPENGLER, BA .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1975, 55 (03) :671-680
[3]   FUNCTIONAL-ANALYSIS OF CHIMERIC GENES OBTAINED BY EXCHANGING HOMOLOGOUS DOMAINS OF THE MOUSE MDR1 AND MDR2 GENES [J].
BUSCHMAN, E ;
GROS, P .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (02) :595-603
[4]  
CHAN HSL, 1988, LAB INVEST, V59, P870
[5]   IMMUNOHISTOCHEMICAL DETECTION OF P-GLYCOPROTEIN - PROGNOSTIC CORRELATION IN SOFT-TISSUE SARCOMA OF CHILDHOOD [J].
CHAN, HSL ;
THORNER, PS ;
HADDAD, G ;
LING, V .
JOURNAL OF CLINICAL ONCOLOGY, 1990, 8 (04) :689-704
[6]   EXPRESSION AND ACTIVITY OF P-GLYCOPROTEIN, A MULTIDRUG EFFLUX PUMP, IN HUMAN HEMATOPOIETIC STEM-CELLS [J].
CHAUDHARY, PM ;
RONINSON, IB .
CELL, 1991, 66 (01) :85-94
[7]  
CHAUDHARY PM, 1992, BLOOD, V80, P2735
[8]   EXPRESSION OF P-GLYCOPROTEIN AND GLUTATHIONE-S-TRANSFERASE IN RECURRENT LYMPHOMAS - THE POSSIBLE ROLE OF EPSTEIN-BARR-VIRUS, IMMUNOPHENOTYPES, AND OTHER PREDISPOSING FACTORS [J].
CHENG, AL ;
SU, IJ ;
CHEN, YC ;
LEE, TC ;
WANG, CH .
JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (01) :109-115
[9]   EXPRESSION OF THE MULTIDRUG RESISTANCE GENE-PRODUCT (P-GLYCOPROTEIN) IN HUMAN NORMAL AND TUMOR-TISSUES [J].
CORDONCARDO, C ;
OBRIEN, JP ;
BOCCIA, J ;
CASALS, D ;
BERTINO, JR ;
MELAMED, MR .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1990, 38 (09) :1277-1287
[10]  
CURT GA, 1984, CANCER TREAT REP, V68, P87