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Serum microRNAs as biomarkers for the therapeutic response to trastuzumab/pertuzumab/taxane therapy in HER2-positive metastatic breast cancer

ABSTRACT: Serum microRNAs profiles of HER2 positive advanced breast cancer patients and their treatment response after the trastuzumab/pertuzumab/taxane therapy

ORGANISM(S): Homo sapiens

PROVIDER: GSE122426 | GEO | 2022/11/04

REPOSITORIES: GEO

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Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2-positive breast cancer in the adaptively randomized I-SPY2 trial.

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

RNA sequencing of BT474 cells treated with trastuzumab or trastuzumab + pertuzumab and BT474-derived cells resistant to trastuzumab or trastuzumab + pertuzumab

Project description:We sequenced untreated BT474 cells, BT474 cells treated for three days with trastuzumab or trastuzumab + pertuzumab, as well as two BT474-derived trastuzumab-resistant pools and two BT474-derived trastuzumab + pertuzumab resistant pools. Resistant pools were generated by culturing BT474 cells in gradually increasing doses of trastuzumab and trastuzumab + pertuzumab over the course of several months and continually maintained in drug.

2020-01-26 | GSE121105 | GEO

Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer

Project description:The purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response. This first comprehensive study of the molecular response to trastuzumab, pertuzumab and combination therapy in vivo highlights that there are both common and distinct downstream effects to different HER2 antibodies and that pathways may be invoked more strongly or in a different manner by a combination of agents. Some of the in vivo results for ovarian tumors differ from previous in vitro studies in breast cancer cells, emphasizing that the molecular response to anti-cancer agents involves variable and complex disease-specific interactions of signaling mechanisms. SCOV3 Ovarian cell line xenografts treated with Trastuzumab, pertuzumab or combination after 4 days

2012-05-02 | E-GEOD-31432 | biostudies-arrayexpress

Identification of resistance mechanisms to anti-HER2 antibody in breast cancer cell line BT-474

Project description:Background: The addition of the anti-HER2 antibody pertuzumab to trastuzumab/chemotherapy treatment in HER2+ breast cancer significantly improves clinical outcome. Concomitantly, the drug-antibody conjugate T-DM1 (trastuzumab-emantasine) has demonstrated efficacy, at least equal, to the combination of trastuzumab/chemotherapy. Scientific, economic and health challenges emerge from the clinical use of these novel anti-HER2 antibodies, aimed to identify new resistance mechanisms and to select the target breast cancer population. Objectives: (1) To identify primary resistance mechanisms to anti-HER2 antibodies trastuzumab, pertuzumab, and to the combined trastuzumab/pertuzumab or pertuzumab/T-DM1 therapy, (2) To identify acquired resistance mechanisms to anti-HER2 antibodies trastuzumab, pertuzumab, and to the combined trastuzumab/pertuzumab or pertuzumab/T-DM1 therapy, (3) To develop new combinations of anti-HER2 antibodies with other targeted therapies.

2019-12-31 | GSE89216 | GEO

Expression profile of HER2-overexpressing CHO cells treated with trastuzumab and pertuzumab

Project description:CHO-K1 (wildtype) and CHO-K6 (stablely overexpressing human HER2) cells were terated with 10 ug/ml transtuzumab or pertuzumab and their combination for 24 h and then the whole gene expression was analyzed by cDNA array.

2018-08-29 | GSE110189 | GEO

Expression profile of HER2-overexpressing CHO cells treated with trastuzumab and pertuzumab

Project description:Expression profile of HER2-overexpressing CHO cells treated with trastuzumab and pertuzumab

| PRJNA433096 | ENA

RNA sequencing of trastuzumab plus pertuzumab-refractory tumor in a mouse xenograft model

Project description:We report RNA sequencing data of trastuzumab plus pertuzumab-refractory tumor in a mouse xenograft model.

2020-03-05 | GSE146380 | GEO

Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer

2012-05-03 | GSE31432 | GEO

RNA sequencing of BT474 cells treated with trastuzumab or trastuzumab + pertuzumab and BT474-derived cells resistant to trastuzumab or trastuzumab + pertuzumab

Project description:RNA sequencing of BT474 cells treated with trastuzumab or trastuzumab + pertuzumab and BT474-derived cells resistant to trastuzumab or trastuzumab + pertuzumab

| PRJNA495653 | ENA

Tumor infiltrating lymphocytes in patients receiving trastuzumab/pertuzumab-based chemotherapy: A TRYPHAENA substudy

Project description:Background: It is critical to identify biomarkers for treatment tailoring in HER2-amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. Patients and methods: Among the 225 patients randomized to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing regimen or concurrently with an anthracycline-free regimen in the Tryphaena trial, we evaluated TILs at baseline in 213 patients of whom 126 with pathological complete response, pCR (ypT0/is ypN0) and 28 with Event Free Survival, EFS events. We computed associations between baseline TILs and either pCR or EFS after adjusting for clinicopathological characteristics using logistic and Cox regression models, respectively. To understand TILs biology, we evaluated associations between baseline TILs and baseline tumor gene expression data (800 gene set by NanoString) in a subset of 173 patients. Results: Among the 213 patients with evaluable TILs at baseline, the median level of TILs was 14% (interquartile range, IQR, 7-32%). After adjusting for clinicopathological characteristics, baseline TILs were not associated with pCR (adjusted odds ratio for every 10% increase in TILs aOR 1.12, 95%CI 0.95-1.31, p=0.17). At a median follow-up of 4.7 years, for every increase in baseline TILs of 10 percentage units there was a 25% reduction in the hazard of the EFS event (adjusted hazard ratio 0.75, 95%CI 0.56-1.00, p=0.05) after adjusting for baseline clinicopathological characteristics and pCR. Genes associated with Epithelial-Mesenchymal Transition (EMT) such as SNAIL1, TWIST1, ZEB1, B7-H3 and NOTCH3 were significantly anti-correlated with TILs. Conclusions: Baseline TILs provide independent prognostic information in patients treated with trastuzumab/pertuzumab-based neoadjuvant chemotherapy. Further validation is needed.

2018-04-01 | GSE109710 | GEO

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