Herceptin Resistance Database for Understanding Mechanism of Resistance in Breast Cancer Patients
نویسندگان
چکیده
Monoclonal antibody Trastuzumab/Herceptin is considered as frontline therapy for Her2-positive breast cancer patients. However, it is not effective against several patients due to acquired or de novo resistance. In last one decade, several assays have been performed to understand the mechanism of Herceptin resistance with/without supplementary drugs. This manuscript describes a database HerceptinR, developed for understanding the mechanism of resistance at genetic level. HerceptinR maintains information about 2500 assays performed against various breast cancer cell lines (BCCs), for improving sensitivity of Herceptin with or without supplementary drugs. In order to understand Herceptin resistance at genetic level, we integrated genomic data of BCCs that include expression, mutations and copy number variations in different cell lines. HerceptinR will play a vital role in i) designing biomarkers to identify patients eligible for Herceptin treatment and ii) identification of appropriate supplementary drug for a particular patient. HerceptinR is available at http://crdd.osdd.net/raghava/herceptinr/.
منابع مشابه
Darpp-32 and Its Truncated Variant t-Darpp Have Antagonistic Effects on Breast Cancer Cell Growth and Herceptin Resistance
BACKGROUND Herceptin (trastuzumab) is a humanized monoclonal antibody that is approved for the treatment of metastatic breast cancer patients whose tumors overexpress Her2 (erbB2/neu). Up to 70% of Her2-positive breast cancers demonstrate a response to Herceptin-based therapies, but resistance almost inevitably arises within a year of the initial response. To help understand the mechanism of He...
متن کامل3, 3′-diindolylmethane Enhances the Effectiveness of Herceptin against HER-2/Neu-Expressing Breast Cancer Cells
Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance d...
متن کاملResistance to HER2-targeted therapy
Production and approval of trastuzumab (Herceptin®) for the treatment of metastatic breast cancer (MBC) was a millstone in antibody-based targeted therapy in the cancer treatment. However, despite the early success in the clinical trials, trastuzumab failed to appreciate the initial attraction due to development of resistance to the drug. The majority of patients who benefit from the drug...
متن کاملSTAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits
Clinically, HER2 proto-oncogene amplification is found in about 25-30% of human breast cancers, where it is correlated to a poor prognosis. Constitutive STAT3 activation is found in about 50-60% of the breast tumors and associated with tumorigenesis and drug resistance. In this study, we showed that STAT3 was phosphorylated in HER2-overexpressing, ER-positive human breast tumors and, furthermor...
متن کاملHER2 Phosphorylation Is Maintained by a PKB Negative Feedback Loop in Response to Anti-HER2 Herceptin in Breast Cancer
Herceptin (trastuzumab) is used in patients with breast cancer who have HER2 (ErbB2)-positive tumours. However, its mechanisms of action and how acquired resistance to Herceptin occurs are still poorly understood. It was previously thought that the anti-HER2 monoclonal antibody Herceptin inhibits HER2 signalling, but recent studies have shown that Herceptin does not decrease HER2 phosphorylatio...
متن کامل