Bypassing cancer drug resistance by activating multiple death pathways - A proposal from the study of circumventing cancer drug resistance by induction of necroptosis

被引:70
作者
Hu, Xun [1 ]
Xuan, Yanyan [1 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Inst Canc, Hangzhou 310027, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; necroptosis; cancer drug resistance;
D O I
10.1016/j.canlet.2007.11.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer drug resistance is a complex, dynamic, and "elusive" system rather than merely a matter of some drug-resistant factors. Current pharmacological approaches aim to restore the efficacy of the standard chemotherapy against drug-resistant cancers via reactivating apoptosis and inhibiting drug transporters, simply because the current available anticancer drugs mostly induce apoptosis and many of them are the substrates/inducers of the drug transporters. However, since there are so many different types of defects in apoptotic pathways as well as numerous drug transporters, which could simultaneously contribute to cancer drug resistance, to succeed in the approach is theoretically possible but practically extremely difficult. To circumvent cancer drug resistance is an alternative choice. Since there are multiple death pathways with molecular mechanisms distinct from each other, we previously proposed that the barriers set up in cancer cells to avoid one pathway were not problems for another. Thus, no matter how dynamic, complex, and "elusive" the resistance occurs along one death pathway (e.g., apoptosis), the resistance would be sequestered within this pathway, and would not affect another death pathway with mechanisms distinct from the former, and vice versa, e.g., apoptotic resistant cancers can be sensitive to an induction of a nonapoptotic death. Indeed, we recently demonstrated that the cancer cells resistant to apoptotic inducers such as anthracycline antibiotics, vinca alkaloids, epipodophylotoxins, were sensitive to necroptotic inducers such as shikonin. Therefore, to bypass cancer drug resistance is principally achievable by simultaneously activating multiple death pathways using combined classes of death inducers (apoptosis, autophagy, necroptosis, etc.). Although each class of death inducers has its own action window and limit in killing cancer cells, a rationalized combination of several classes of death inducers that compliment each other would maximize their efficacy while simultaneously minimizing their weakness. Such "mixed bullets" would probably achieve a good therapeutic efficacy by bypassing cancer drug resistance. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:127 / 137
页数:11
相关论文
共 63 条
[1]   Biochemical, cellular, and pharmacological aspects of the multidrug transporter [J].
Ambudkar, SV ;
Dey, S ;
Hrycyna, CA ;
Ramachandra, M ;
Pastan, I ;
Gottesman, MM .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1999, 39 :361-398
[2]   Analysis of APAF-1 expression in human cutaneous melanoma progression [J].
Baldi, A ;
Santini, D ;
Russo, P ;
Catricalà, C ;
Amantea, A ;
Picardo, M ;
Tatangelo, F ;
Botti, G ;
Dragonetti, E ;
Murace, R ;
Tonini, G ;
Natali, PG ;
Baldi, F ;
Paggi, MG .
EXPERIMENTAL DERMATOLOGY, 2004, 13 (02) :93-97
[3]   Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice [J].
Bargou, RC ;
Wagener, C ;
Bommert, K ;
Mapara, MY ;
Daniel, PT ;
Arnold, W ;
Dietel, M ;
Guski, H ;
Feller, A ;
Royer, HD ;
Dorken, B .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (11) :2651-2659
[4]   Downregulation of proapoptotic proteins Bax and Bcl-Xs in p53 overexpressing hepatocellular carcinomas [J].
Beerheide, W ;
Tan, YJ ;
Teng, E ;
Ting, AE ;
Jedpiyawongse, A ;
Srivatanakul, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 273 (01) :54-61
[5]   Opinion - The role of apoptosis in cancer development and treatment response [J].
Brown, JM ;
Attardi, LD .
NATURE REVIEWS CANCER, 2005, 5 (03) :231-237
[6]   Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy [J].
Buchholz, TA ;
Davis, DW ;
McConkey, DJ ;
Symmans, WF ;
Valero, V ;
Jhingran, A ;
Tucker, SL ;
Pusztai, L ;
Cristofanilli, M ;
Esteva, FJ ;
Hortobagyi, GN ;
Sahin, AA .
CANCER JOURNAL, 2003, 9 (01) :33-41
[7]   Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump [J].
Burger, H ;
van Tol, H ;
Boersma, AWM ;
Brok, M ;
Wiemer, EAC ;
Stoler, G ;
Nooter, K .
BLOOD, 2004, 104 (09) :2940-2942
[8]   Triggering and modulation of apoptosis by oxidative stress [J].
Chandra, J ;
Samali, A ;
Orrenius, S .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 29 (3-4) :323-333
[9]   An improved method for rapid generation of unmarked Pseudomonas aeruginosa deletion mutants -: art. no. 30 [J].
Choi, KH ;
Schweizer, HP .
BMC MICROBIOLOGY, 2005, 5 (1)
[10]   OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE [J].
COLE, SPC ;
BHARDWAJ, G ;
GERLACH, JH ;
MACKIE, JE ;
GRANT, CE ;
ALMQUIST, KC ;
STEWART, AJ ;
KURZ, EU ;
DUNCAN, AMV ;
DEELEY, RG .
SCIENCE, 1992, 258 (5088) :1650-1654