Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA208626 | ENA |
REPOSITORIES: ENA
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Project description:The clinical relevance of tumor infiltrating lymphocytes (TILs) in breast cancer (BC) is not firmly established. We aimed to validate previous prognostic findings in triple negative breast cancer (TNBC) and investigate predictive associations with trastuzumab benefit in HER2 overexpressing disease (HER2+).
2022-07-16 | GSE47994 | GEO
Project description:The human epidermal growth factor receptor 2 (HER2) gene encodes a tyrosine kinase receptor that controls important signal transduction pathways in breast cancer. Amplification and overexpression of the HER2 gene occurs in approximately 20% of breast cancers and is associated with an aggressive clinical phenotype. Trastuzumab, a humanized monoclonal antibody that targets HER2 showed exceptional efficacy in the treatment of breast cancer. In the adjuvant treatment of breast cancer patients, five randomized trials showed significant benefit of trastuzumab, with a reduction in the rate of recurrence of approximately 50% and improvement in the rate of survival of approximately 30%. In the current study, positive early stage breast cancer samples treated with adjuvant trastuzumab provided by institute Jules Bordet (IJB) and KUL. Gene expression and clinical outcome data were available. to better understand the genetic regulations and effects of the trastuzumab, we profile the the genes expression of positive early stage breast cancer samples treated with adjuvant trastuzumab.
2016-12-31 | GSE58984 | GEO
Project description:Ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel plus trastuzumab and pertuzumab (THP) are two of the experimental regiments evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer. In pre-defined analyses we assessed 10 biomarkers at the pre-treatment timepoint in the HER2, ER/PR, and proliferation pathways to test their association with pCR (complete pathologic response).
2021-08-24 | GSE181574 | GEO
Project description:Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX) on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H).
2012-12-11 | GSE42822 | GEO
Project description:Monoclonal antibodies (mAbs) targeting the oncogenic receptor tyrosine kinase ERBB2/HER2, such as Trastuzumab, are the standard of care therapy for breast cancers driven by ERBB2 overexpression and activation. However, a substantial proportion of patients exhibits de novo resistance. Here, by comparing matched Trastuzumab-naïve and post-treatment patient samples from a neoadjuvant trial, we link resistance with elevation of H3K27me3, a repressive histone modification catalyzed by Polycomb Repressor Complex 2 (PRC2). In ErbB2+ breast cancer models, PRC2 silences endogenous retroviruses (ERVs) to suppress anti-tumor Type-I interferon (IFN) responses. In patients, elevated H3K27me3 in tumor cells following Trastuzumab treatment correlates with suppression of IFN-driven viral defense gene expression signatures and poor response. Using an immunocompetent model, we provide evidence that EZH2 inhibitors promote IFN-driven immune responses that enhance the efficacy of anti-ErbB2 mAbs, suggesting the potential clinical benefit of epigenomic reprogramming by H3K27me3 depletion in Trastuzumab-resistant disease.
2019-08-23 | GSE136205 | GEO
Project description:Monoclonal antibodies (mAbs) targeting the oncogenic receptor tyrosine kinase ERBB2/HER2, such as Trastuzumab, are the standard of care therapy for breast cancers driven by ERBB2 overexpression and activation. However, a substantial proportion of patients exhibits de novo resistance. Here, by comparing matched Trastuzumab-naïve and post-treatment patient samples from a neoadjuvant trial, we link resistance with elevation of H3K27me3, a repressive histone modification catalyzed by Polycomb Repressor Complex 2 (PRC2). In ErbB2+ breast cancer models, PRC2 silences endogenous retroviruses (ERVs) to suppress anti-tumor Type-I interferon (IFN) responses. In patients, elevated H3K27me3 in tumor cells following Trastuzumab treatment correlates with suppression of IFN-driven viral defense gene expression signatures and poor response. Using an immunocompetent model, we provide evidence that EZH2 inhibitors promote IFN-driven immune responses that enhance the efficacy of anti-ErbB2 mAbs, suggesting the potential clinical benefit of epigenomic reprogramming by H3K27me3 depletion in Trastuzumab-resistant disease.
2019-08-22 | GSE136157 | GEO
Project description:Monoclonal antibodies (mAbs) targeting the oncogenic receptor tyrosine kinase ERBB2/HER2, such as Trastuzumab, are the standard of care therapy for breast cancers driven by ERBB2 overexpression and activation. However, a substantial proportion of patients exhibits de novo resistance. Here, by comparing matched Trastuzumab-naïve and post-treatment patient samples from a neoadjuvant trial, we link resistance with elevation of H3K27me3, a repressive histone modification catalyzed by Polycomb Repressor Complex 2 (PRC2). In ErbB2+ breast cancer models, PRC2 silences endogenous retroviruses (ERVs) to suppress anti-tumor Type-I interferon (IFN) responses. In patients, elevated H3K27me3 in tumor cells following Trastuzumab treatment correlates with suppression of IFN-driven viral defense gene expression signatures and poor response. Using an immunocompetent model, we provide evidence that EZH2 inhibitors promote IFN-driven immune responses that enhance the efficacy of anti-ErbB2 mAbs, suggesting the potential clinical benefit of epigenomic reprogramming by H3K27me3 depletion in Trastuzumab-resistant disease.
2019-08-26 | GSE136300 | GEO
Project description:Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX) on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H). Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to affymetrix microarrays according to manufacturer protocol.
2012-12-11 | E-GEOD-42822 | biostudies-arrayexpress
Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.
2024-02-14 | PXD031794 | Pride
Project description:Background: Central nervous system (CNS) metastases represent a major problem in the treatment of HER2-positive breast cancer due to the disappointing efficacy of HER2-targeted therapies in the brain microenvironment. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in preclinical models of brain metastases. Methods: We treated mice bearing BT474 or MDA-MB-361 tumors in the CNS (N=9-11 per group), or cancer cells grown in organotypic brain slice cultures with trastuzumab or T-DM1 at equivalent or equipotent doses. Using intravital imaging, molecular techniques and histological analysis we determined tumor growth, mouse survival, cancer cell apoptosis and proliferation, tumor drug distribution, and HER2 signaling. All statistical tests were two-sided. Results: T-DM1 significantly delayed the growth of HER2-positive breast cancer brain metastases compared to trastuzumab. These findings were consistent between HER2-driven and PI3K-driven tumors. The activity of T-DM1 resulted in a striking survival benefit (median survival for BT474 tumors: 28d for trastuzumab vs 112d for T-DM1, HR=6.2, 95% CI=6.1 to 85.84; P<.001). No difference in drug distribution and HER2-signaling was revealed between the two groups. However, T-DM1 led to a significant increase in tumor cell apoptosis (One-way ANOVA for ApopTag, p<.001), which was associated with mitotic catastrophe. Conclusions: T-DM1 can overcome resistance to trastuzumab therapy in HER2-driven and PI3K-driven breast cancer brain lesions due to the cytotoxicity of the DM1 component. Clinical investigation of T-DM1 for patients with CNS metastases from HER2-positive breast cancer is warranted. Comparison of trastuzumab (n=4) and TDM-1 (n=4) treated BT-474 human breast carcinoma cells growing in murine brain
2015-11-09 | E-GEOD-69042 | biostudies-arrayexpress