Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy Journal Article
| Authors: | Parra-Palau, J. L.; Morancho, B.; Peg, V.; Escorihuela, M.; Scaltriti, M.; Vicario, R.; Zacarias-Fluck, M.; Pedersen, K.; Pandiella, A.; Nuciforo, P.; Serra, V.; Cortés, J.; Baselga, J.; Perou, C. M.; Prat, A.; Rubio, I. T.; Arribas, J. |
| Article Title: | Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy |
| Abstract: | Human epidermal growth factor receptor 2 (HER2) positive breast cancers are currently treated with trastuzumab, an anti-HER2 antibody. About 30% of these tumors express a group of HER2 fragments collectively known as p95HER2. Our previous work indicated that p95HER2-positive tumors are resistant to trastuzumab monotherapy. However, recent results showed that tumors expressing the most active of these fragments, p95HER2/611CTF, respond to trastuzumab plus chemotherapy. To clarify this discrepancy, we analyzed the response to chemotherapy of cell lines transfected with p95HER2/611CTF and patient-derived xenografts (n = 7 mice per group) with different levels of the fragment. All statistical tests were two-sided. p95HER2/611CTFnegative and positive tumors showed different responses to various chemotherapeutic agents, which are particularly effective on p95HER2/611CTF-positive cells. Furthermore, chemotherapy sensitizes p95HER2/611CTF-positive patient-derived xenograft tumors to trastuzumab (mean tumor volume, trastuzumab alone: 906 mm3, 95% confidence interval = 1274 to 538 mm3; trastuzumab+doxorubicin: 259 mm3, 95% confidence interval = 387 to 131 mm3; P .001). This sensitization may be related to HER2 stabilization induced by chemotherapy in p95HER2/611CTF-positive cells. © The Author 2014. |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 106 |
| Issue: | 11 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 2014-09-24 |
| Start Page: | dju291 |
| Language: | English |
| DOI: | 10.1093/jnci/dju291 |
| PROVIDER: | scopus |
| PMCID: | PMC4271027 |
| PUBMED: | 25253614 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2016 -- Source: Scopus |
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