Molecular mechanisms of platinum resistance: still searching for the Achilles' heel

被引:89
作者
Wernyj, RP [1 ]
Morin, PJ [1 ]
机构
[1] NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA
关键词
drug resistance; platinum compounds; cisplatin; resistance mechanisms; MUC1;
D O I
10.1016/j.drup.2004.08.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The platinum compounds cisplatin and carboplatin are commonly used in cancer chemotherapy. However, tumors frequently develop resistance to these compounds, significantly decreasing their usefulness in the clinic. In the past few years, basic research has unraveled novel and unexpected mechanisms for the development of platinum resistance. For example, it has been reported that MUC1 expression and particularly the localization of its C-terminal subunit to the mitochondria may affect cisplatin resistance. Another recent finding suggests that cisplatin damage may activate DNA-dependent protein kinase (DNA-PK) to initiate a death signal that can be transmitted to neighboring cells through gap junctions, adding to a growing belief that the interactions of cancer cells with their surroundings may be important to the outcome of chemotherapy. While most clinical efforts have focused on identifying alternative regimens for drug-resistant cancer, it might be possible to exploit our knowledge of the mechanism of platinum resistance to specifically reverse resistance and increase platinum efficacy. The strategy of drug resistance reversal therapy (DRRT) may have significant impact on our approaches to the treatment and management of drug-resistant tumors. Published by Elsevier Ltd.
引用
收藏
页码:227 / 232
页数:6
相关论文
共 68 条
[1]  
Adjei AA, 2003, CLIN CANCER RES, V9, P2520
[2]   Ovarian cancer: Strategies for overcoming resistance to chemotherapy [J].
Agarwal, R ;
Kaye, SB .
NATURE REVIEWS CANCER, 2003, 3 (07) :502-516
[3]   Preclinical studies with erlotinib (Tarceva) [J].
Akita, RW ;
Sliwkowski, MX .
SEMINARS IN ONCOLOGY, 2003, 30 (03) :15-24
[4]  
ANDREWS PA, 1987, CANCER CHEMOTH PHARM, V19, P149
[5]   Phase II study of docetaxel-vinorelbine in platinum-resistant, paclitaxel-pretreated ovarian cancer [J].
Aravantinos, G ;
Bafaloukos, D ;
Fountzilas, G ;
Christodoulou, C ;
Papadimitriou, C ;
Pavlidis, N ;
Kalofonos, HP ;
Gogas, H ;
Kosmidis, P ;
Dimopoulos, MA .
ANNALS OF ONCOLOGY, 2003, 14 (07) :1094-1099
[6]   Enhanced sensitivity and long-term G2 arrest in hydrogen peroxide-treated Ku80-Null cells are unrelated to DNA repair defects [J].
Arrington, ED ;
Caldwell, MC ;
Kumaravel, TS ;
Lohani, A ;
Joshi, A ;
Evans, MK ;
Chen, HT ;
Nussenzweig, A ;
Holbrook, NJ ;
Gorospe, M .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 29 (11) :1166-1176
[7]   Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer [J].
Baekelandt, M ;
Lehne, G ;
Tropé, CG ;
Szántó, I ;
Pfeiffer, P ;
Gustavssson, B ;
Kristensen, GB .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (12) :2983-2993
[8]   Drug resistance reversal - are we getting closer? [J].
Baird, RD ;
Kaye, SB .
EUROPEAN JOURNAL OF CANCER, 2003, 39 (17) :2450-2461
[9]   Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin [J].
Baselga, J ;
Pfister, D ;
Cooper, MR ;
Cohen, R ;
Burtness, B ;
Bos, M ;
D'Andrea, G ;
Seidman, A ;
Norton, L ;
Gunnett, K ;
Falcey, J ;
Anderson, V ;
Waksal, H ;
Mendelsohn, J .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (04) :904-914
[10]  
Bhargava P, 2001, CLIN CANCER RES, V7, P3912