Stemming Resistance to HER-2 Targeted Therapy

被引：55

作者：

Bedard, Philippe L. ^{[2
]}

Cardoso, Fatima ^{[2
,3
]}

Piccart-Gebhart, Martine J. ^{[1
,2
,3
]}

机构：

[1] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium

[2] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium

[3] Univ Libre Bruxelles, Brussels, Belgium

来源：

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA | 2009年 / 14卷 / 01期

关键词：

Breast neoplasms; erbB-2; receptor; Monoclonal antibodies; Protein-tyrosine kinases; Cancer stem cells; BREAST-CANCER CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; TRASTUZUMAB RESISTANCE; PREOPERATIVE TRASTUZUMAB; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; INITIATING CELLS; TUMOR-METASTASIS; MOUSE MODELS; RECEPTOR;

D O I：

10.1007/s10911-009-9116-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Although the development of trastuzumab and lapatinib has improved the outlook for women with HER-2 positive breast cancer, resistance to HER-2 targeted therapy is a growing clinical dilemma. Recent evidence indicates that the HER-2 pathway may play an important role in the maintenance of cancer stem cells (CSCs). The success of HER-2 targeted therapies may, in part, be explained by their direct activity against HER-2 positive CSCs. Our understanding of the mechanisms involved in resistance to trastuzumab, including loss or blockade of the trastuzumab binding site, activation of alternative signaling pathways, and induction of epithelial-mesenchymal transition (EMT), suggests that CSCs may be at the root of resistance of HER-2 targeted therapy. A variety of novel HER-2 targeted approaches have demonstrated promising preliminary clinical activity. Future clinical trials should involve the integration of technologies to assess the impact of novel HER-2 targeted therapies on HER-2 positive CSCs.

引用

页码：55 / 66

页数：12

共 93 条

[21] Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer [J].

Dowsett, M .

[22] Phosphatidylinositol 3-Kinase Hyperactivation Results in Lapatinib Resistance that Is Reversed by the mTOR/Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235 [J].

Eichhorn, Pieter J. A. ;

Gili, Magui ;

Scaltriti, Maurizio ;

Serra, Violeta ;

Guzman, Marta ;

Nijkamp, Wouter ;

Beijersbergen, Roderick L. ;

Valero, Vanesa ;

Seoane, Joan ;

Bernards, Rene ;

Baselga, Jose .

CANCER RESEARCH, 2008, 68 (22) :9221-9230

[23] Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer [J].

Esteva, FJ ;

Valero, V ;

Booser, D ;

Guerra, LT ;

Murray, JL ;

Pusztai, L ;

Cristofanilli, M ;

Arun, B ;

Esmaeli, B ;

Fritsche, HA ;

Sneige, N ;

Smith, TL ;

Hortobagyi, GN .

JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (07) :1800-1808

[24] CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer [J].

Esteva, Francisco J. ;

Wang, Jing ;

Lin, Feng ;

Mejia, Jaime A. ;

Yan, Kai ;

Altundag, Kadri ;

Valero, Vicente ;

Buzdar, Aman U. ;

Hortobagyi, Gabriel N. ;

Symmans, W. Fraser ;

Pusztai, Lajos .

BREAST CANCER RESEARCH, 2007, 9 (06)

[25] Survival of the fittest: Cancer stem cells in therapeutic resistance and angiogenesis [J].

Eyler, Christine E. ;

Rich, Jeremy N. .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (17) :2839-2845

[26]

GELMON KA, 2008, AM SOC CLIN ONC 2008

[27] Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2 [J].

Gennari, R ;

Menard, S ;

Fagnoni, F ;

Ponchio, L ;

Scelsi, M ;

Tagliabue, E ;

Castiglioni, F ;

Villani, L ;

Magalotti, C ;

Gibelli, N ;

Oliviero, B ;

Ballardini, B ;

Da Prada, G ;

Zambelli, A ;

Costa, A .

CLINICAL CANCER RESEARCH, 2004, 10 (17) :5650-5655

[28] Lapatinib plus capecitabine for HER2-positive advanced breast cancer [J].

Geyer, Charles E. ;

Forster, John ;

Lindquist, Deborah ;

Chan, Stephen ;

Romieu, C. Gilles ;

Pienkowski, Tadeusz ;

Jagiello-Gruszfeld, Agnieszka ;

Crown, John ;

Chan, Arlene ;

Kaufman, Bella ;

Skarlos, Dimosthenis ;

Campone, Mario ;

Davidson, Neville ;

Berger, Mark ;

Oliva, Cristina ;

Rubin, Stephen D. ;

Stein, Steven ;

Cameron, David .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (26) :2733-2743

[29] Hyaluronan constitutively regulates ErbB2 phosphorylation and signaling complex formation in carcinoma cells [J].

Ghatak, S ;

Misra, S ;

Toole, BP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (10) :8875-8883

[30] ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome [J].

Ginestier, Christophe ;

Hur, Min Hee ;

Charafe-Jauffret, Emmanuelle ;

Monville, Florence ;

Dutcher, Julie ;

Brown, Marty ;

Jacquemier, Jocelyne ;

Viens, Patrice ;

Kleer, Celina G. ;

Liu, Suling ;

Schott, Anne ;

Hayes, Dan ;

Birnbaum, Daniel ;

Wicha, Max S. ;

Dontu, Gabriela .

CELL STEM CELL, 2007, 1 (05) :555-567

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