Mechanisms of resistance to aromatase inhibitors

被引：50

作者：

Dowsett, M ^{[1
]}

Martin, LA

Smith, I

Johnston, S

机构：

[1] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England

[2] Breakthrough Breast Canc Ctr, Chester Beatty Labs, London SW3 6JB, England

[3] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2005年 / 95卷 / 1-5期

关键词：

aromatase inhibitor; oestrogen receptor; anastrozole; letrozole; resistance;

D O I：

10.1016/j.jsbmb.2005.04.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aromatase inhibitors are rapidly becoming the first choice for hormonal treatment of steroid receptor positive breast cancer in postmenopausal women. An understanding of the resistance mechanisms to these agents is, therefore, important for the appropriate delivery of treatment to responsive patients and the rational development of new agents targeted at the resistance pathways. De novo resistance appears to be a quantitative rather than qualitative phenomenon with virtually all oestrogen receptor positive tumours showing an anti-proliferative response to the aromatase inhibitor anastrozole. While the expression of type I growth factor receptors reduces response to tamoxifien this appears to have little detrimental effect on response to aromatase inhibitors. Studies of acquired resistance in vitro have indicated that acquisition of hypersensitivity to oestrogenic stimulation is a key mechanism that is dependent on enhanced cross-talk of growth factor and oestrogen signaling pathways. Collection of resistant biopsy tissues from patients is important to determine if this mechanism is clinically relevant. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：167 / 172

页数：6

共 25 条

[1] AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer [J].

Anzick, SL ;

Kononen, J ;

Walker, RL ;

Azorsa, DO ;

Tanner, MM ;

Guan, XY ;

Sauter, G ;

Kallioniemi, OP ;

Trent, JM ;

Meltzer, PS .

SCIENCE, 1997, 277 (5328) :965-968

[2] Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer [J].

Buzdar, AU .

ONCOLOGIST, 2003, 8 (04) :335-341

[3] Molecular changes associated with the acquisition of oestrogen hypersensitivity in MCF-7 breast cancer cells on long-term oestrogen deprivation [J].

Chan, CMW ;

Martin, LA ;

Johnston, SRD ;

Ali, S ;

Dowsett, M .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2002, 81 (4-5) :333-341

[4]

Clarke M, 1998, LANCET, V351, P1451

[5]

Coutts AS, 1998, CANCER RES, V58, P4071

[6] AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor [J].

de Mora, JF ;

Brown, M .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (14) :5041-5047

[7]

DOWSETT J, IN PRESS ANN ONCOL

[8] AROMATIZATION INHIBITION ALONE OR IN COMBINATION WITH GNRH AGONISTS FOR THE TREATMENT OF PREMENOPAUSAL BREAST-CANCER PATIENTS [J].

DOWSETT, M ;

STEIN, RC ;

COOMBES, RC .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1992, 43 (1-3) :155-159

[9]

Dowsett M, 2005, CLIN CANCER RES, V11, p951S

[10]

Dowsett M, 2003, BREAST CANCER RES TR, V82, pS7

← 1 2 3 →