Cardiotoxicity of the new cancer therapeutics -: mechanisms of, and approaches to, the problem

被引:64
作者
Force, Thomas [1 ]
Kerkelae, Risto [1 ]
机构
[1] Thomas Jefferson Univ, Jefferson Med Coll, Ctr Translat Med, Philadelphia, PA 19107 USA
关键词
D O I
10.1016/j.drudis.2008.05.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cardiotoxicity of some targeted therapeutics, including monoclonal antibodies and small-molecule inhibitors, is a reality. Herein we will examine why it occurs, focusing on molecular mechanisms to better understand the issue. We will also examine how big the problem is and, more importantly, how big it may become in the future. We will review models for detecting cardiotoxicity in the preclinical phase. We will also focus on two key areas that drive cardiotoxicity: multitargeting and the inherent lack of selectivity of ATP-competitive antagonists. Finally, we will examine the issue of reversibility and discuss possible approaches to keeping patients on therapy.
引用
收藏
页码:778 / 784
页数:7
相关论文
共 51 条
[41]   Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo [J].
Sebolt-Leopold, JS ;
Dudley, DT ;
Herrera, R ;
Van Becelaere, K ;
Wiland, A ;
Gowan, RC ;
Tecle, H ;
Barrett, SD ;
Bridges, A ;
Przybranowski, S ;
Leopold, WR ;
Saltiel, AR .
NATURE MEDICINE, 1999, 5 (07) :810-816
[42]   Cardiac dysfunction in the trastuzumab clinical trials experience [J].
Seidman, A ;
Hudis, C ;
Pierri, MK ;
Shak, S ;
Paton, V ;
Ashby, M ;
Murphy, M ;
Stewart, SJ ;
Keefe, D .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (05) :1215-1221
[43]   Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency [J].
Shah, Neil P. ;
Skaggs, Brian J. ;
Branford, Susan ;
Hughes, Timothy P. ;
Nicoll, John M. ;
Paquette, Ronald L. ;
Sawyers, Charles L. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (09) :2562-2569
[44]   Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure [J].
Shiojima, I ;
Sato, K ;
Izumiya, Y ;
Schiekofer, S ;
Ito, M ;
Liao, RL ;
Colucci, WS ;
Walsh, K .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (08) :2108-2118
[45]   Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. [J].
Slamon, DJ ;
Leyland-Jones, B ;
Shak, S ;
Fuchs, H ;
Paton, V ;
Bajamonde, A ;
Fleming, T ;
Eiermann, W ;
Wolter, J ;
Pegram, M ;
Baselga, J ;
Norton, L .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (11) :783-792
[46]   HUMAN-BREAST CANCER - CORRELATION OF RELAPSE AND SURVIVAL WITH AMPLIFICATION OF THE HER-2 NEU ONCOGENE [J].
SLAMON, DJ ;
CLARK, GM ;
WONG, SG ;
LEVIN, WJ ;
ULLRICH, A ;
MCGUIRE, WL .
SCIENCE, 1987, 235 (4785) :177-182
[47]   Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells [J].
Spector, Neil L. ;
Yarden, Yosef ;
Smith, Bradley ;
Lyass, Ljuba ;
Trusk, Patricia ;
Pry, Karen ;
Hill, Jason E. ;
Xia, Wenle ;
Seger, Rony ;
Bacus, Sarah S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (25) :10607-10612
[48]   Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31 [J].
Tan-Chiu, E ;
Yothers, G ;
Romond, E ;
Geyer, CE ;
Ewer, M ;
Keefe, D ;
Shannon, RP ;
Swain, SM ;
Brown, A ;
Fehrenbacher, L ;
Vogel, VG ;
Seay, TE ;
Rastogi, P ;
Mamounas, EP ;
Wolmark, N ;
Bryant, J .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (31) :7811-7819
[49]   Trastuzumab-related cardiotoxicity: Calling into question the concept of reversibility [J].
Telli, Melinda L. ;
Hunt, Sharon A. ;
Carlson, Robert W. ;
Guardino, Alice E. .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (23) :3525-3533
[50]  
VIA MC, 2007, INSIGHT PHARM REPORT