| | |  | | | | Record from Web of Science® | | | | | | |
| PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients |
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| Author(s): Nagata Y, Lan KH, Zhou XY, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu DH |
| Source: CANCER CELL Volume: 6 Issue: 2 Pages: 117-127 Published: AUG 2004 |
| Times Cited: 366 References: 61 |
| Abstract: The ErbB2-targeting antibody, trastuzumab (Herceptin), has remarkable therapeutic efficacy in certain patients with ErbB2-overexpressing tumors. The overall trastuzumab response rate, however, is limited and what determines trastuzumab response is poorly understood. Here we report that PTEN activation contributes to trastuzumab's antitumor activity. Trastuzumab treatment quickly increased PTEN membrane localization and phosphatase activity by reducing PTEN tyrosine phosphorylation via Src inhibition. Reducing PTEN in breast cancer cells by antisense oligonucleotides conferred trastuzumab resistance in vitro and in vivo. Patients with PTEN-deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal PTEN. Thus, PTEN deficiency is a powerful predictor for trastuzumab resistance. Additionally, PI3K inhibitors rescued PTEN loss-induced trastuzumab resistance, suggesting that PI3K-targeting therapies could overcome this resistance. |
| Document Type: Article |
| Language: English |
| Reprint Address: Yu, DH (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA |
Addresses:
1. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA
2. Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA
3. Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA
4. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
5. ISIS Pharmaceut, Carlsbad, CA 92008 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Oncology |
| IDS Number: 850DR |
| ISSN: 1535-6108 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |