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| Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients |
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| Author(s): Aas T, Borresen AL, Geisler S, SmithSorensen B, Johnsen H, Varhaug JE, Akslen LA, Lonning PE |
| Source: NATURE MEDICINE Volume: 2 Issue: 7 Pages: 811-814 Published: JUL 1996 |
| Times Cited: 448 References: 18 |
| Abstract: The mechanisms causing resistance to chemotherapeutic drugs in cancer patients are poorly understood. Recent evidence suggests that different forms of chemotherapy may exert their cytotoxic effects by inducing apoptosis(1). The tumor suppressor gene P53 has a pivotal role inducing apoptosis in response to cellular damage. In vitro investigations have shown intact p53 to play a critical role executing cell death in response to treatment with cytotoxic drugs like 5-fluorouracil, etoposide and doxorubicin(2). Recently, mutations in the P53 gene were found to confer resistance to anthracyclines in a mouse sarcoma tumor model(3) and overexpression of the p53 protein (which, in most cases, is due to a mutated gene) was found to be associated with lack of response to cisplatin-based chemotherapy in non-small cell lung cancer(4). Previous studies have shown mutations in the P53 gene or overexpression of the p53 protein to predict a poor prognosis(5-7), but also a beneficial effect of adjuvant radiotherapy(8) or chemotherapy(9) in breast cancer. In this study we present data linking specific mutations in the P53 gene to primary resistance to doxorubicin therapy and early relapse in breast cancer patients. |
| Document Type: Article |
| Language: English |
Addresses:
1. NORWEGIAN RADIUMHOSP, DEPT GENET, N-0310 MONTEBELLO, OSLO NORWAY
2. HAUKELAND UNIV HOSP, DEPT ONCOL, N-5021 BERGEN, NORWAY
3. GADE INST, DEPT SURG, N-5021 BERGEN, NORWAY
4. GADE INST, DEPT PATHOL, N-5021 BERGEN, NORWAY |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: UU680 |
| ISSN: 1078-8956 |
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