The role of genetic variability in drug metabolism pathways in breast cancer prognosis

被引:35
作者
Choi, Ji-Yeob
Nowell, Susan A.
Blanco, Javier G.
Ambrosone, Christine B.
机构
[1] Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA
[2] Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA
[3] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA
关键词
anthracyclines; aromatase inhibitors; breast cancer; cyclophosphamide; pharmacogenetics; single nucleotide polymorphisms; tamoxifen; taxanes;
D O I
10.2217/14622416.7.4.613
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Among patients receiving adjuvant therapy for breast cancer, there is variability in treatment outcomes, and it is unclear which patients will receive the most benefit from treatment and which will have better disease-free survival. To date, most studies of breast cancer prognosis have focused on tumor characteristics, but it is likely that pharmacogenetics, genetic variability in the metabolism of therapeutic agents, also plays a role in the prediction of survival. in this paper, we briefly discuss the metabolic pathways of drugs commonly used for the treatment of breast cancer (cyclophosphamide, doxorubicin, taxanes, tamoxifen and aromatase inhibitors) and describe the known genetic variants that may impact those pathways. Studies that have evaluated potential effects of these genetic variants on treatment outcomes are also discussed. It is likely that the application of pharmacogenetics, particularly in the setting of randomized clinical trials, will contribute to findings that may result in individualized therapeutic dosing.
引用
收藏
页码:613 / 624
页数:12
相关论文
共 94 条
  • [1] Abe O, 1998, LANCET, V352, P930
  • [2] AHN J, 2006, IN PRESS CANC EPIDEM
  • [3] Ambrosone CB, 1999, CANCER RES, V59, P602
  • [4] Ambrosone CB, 2005, CANCER RES, V65, P1105
  • [5] Ambrosone CB, 2001, CANCER RES, V61, P7130
  • [6] A single nucleotide polymorphism of CYP2B6 found in Japanese enhances catalytic activity by autoactivation
    Ariyoshi, N
    Miyazaki, M
    Toide, K
    Sawamura, Y
    Kamataki, T
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 281 (05) : 1256 - 1260
  • [7] AUSTIN GE, 1993, LEUKEMIA, V7, P1445
  • [8] CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel 6α-hydroxylase activity in human liver microsomes
    Bahadur, N
    Leathart, JBS
    Mutch, E
    Steimel-Crespi, D
    Dunn, SA
    Gilissen, R
    Van Houdt, J
    Hendrickx, J
    Mannens, G
    Bohets, H
    Williams, FM
    Armstrong, M
    Crespi, CL
    Daly, AK
    [J]. BIOCHEMICAL PHARMACOLOGY, 2002, 64 (11) : 1579 - 1589
  • [9] Structural and functional characterisation of human sulfotransferases
    Brix, LA
    Nicoll, R
    Zhu, XY
    McManus, ME
    [J]. CHEMICO-BIOLOGICAL INTERACTIONS, 1998, 109 (1-3) : 123 - 127
  • [10] CLARKE L, 1989, CANCER RES, V49, P2344