Epi Tax targeted sequencing
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ABSTRACT:
PROVIDER: EGAS00001000587 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Sequencing of 350 cancer genes in BC samples from patients treated with either Epirubicin or Paclitaxel monotherapy in the neoadjuvant setting.
| EGAD00001000812 | EGA
Project description:PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant TOP trial, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase IIα (TOP2A) and to develop a gene expression signature to identify those patients who do not benefit from anthracyclines. METHODS: The TOP trial included 149 patients, of which 141 were evaluable for response prediction analyses. The primary endpoint was pathological complete response (pCR). TOP2A and gene expression profiles were evaluated using pre-epirubicin biopsies. Gene expression data from ER-negative samples of the EORTC 10994/BIG 00-01 and MDACC 2003-0321 neoadjuvant trials were used for validation purposes. RESULTS: A pCR was obtained in 14% of the evaluable TOP patients. TOP2A amplification, but not protein overexpression, was significantly associated with pCR (p=0.001 and 0.22). We developed an “anthracycline-based score (A-Score)” that combines three signatures: a TOP2A gene signature and two previously published signatures related to tumor invasion and immune response. The A-Score was characterized by a high negative predictive value (NPV=0.98 [95% CI: 0.90-1.00]) overall, and in the HER2-negative and HER2-positive subpopulations. Its performance was independently confirmed in the anthracycline-based (FAC/FEC) arms of the two validation trials (BIG 00-01: 0.80 [0.61-0.92] and MDACC 2003-0321: 1.00 [0.80-1.00]). CONCLUSION: Given its high NPV, the A-Score could become, if further validated, a useful clinical tool to identify those patients who do not benefit from anthracyclines and could therefore be spared the non-negligible side effects. Predicting the efficacy of anthracyclines (epirubicin) in breast cancer (BC) patients (TOP trial) 120 microarray experiments from primary ER-negative breast tumors of anthracycline-treated patients. No replicate, no reference sample.
2010-01-26 | E-GEOD-16446 | biostudies-arrayexpress
Project description:Background: Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30-40% of ER+BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings. Results: We developed a gene classifier consisting of 181 genes belonging to 13 biological clusters. In the independent set of adjuvantly-treated samples, it was able to define two distinct prognostic groups (HR 2.01 95%CI: 1.29-3.13; p=0.002). Six of the 13 gene clusters represented pathways involved in cell cycle and proliferation. In 112 metastatic breast cancer patients treated with tamoxifen, one of the classifier components suggesting a cellular inflammatory mechanism was significantly predictive of response. Conclusions: We have developed a gene classifier that can predict clinical outcome in tamoxifen-treated ER+ BC patients. Whilst our study emphasizes the important role of proliferation genes in prognosis, our approach proposes other genes and pathways that may elucidate further mechanisms that influence clinical outcome and prediction of response to tamoxifen. Experiment Overall Design: dataset of microarray experiments from primary breast tumors of patients treated by Tamoxifen in adjuvant setting. No replicate, no reference sample.
2008-06-20 | E-GEOD-9195 | biostudies-arrayexpress
Project description:Intrinsic and acquired resistance to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) remains a major barrier in treating homologous recombination (HR) repair-deficient tumors, including those with germline or somatic BRCA1/2 mutations. Although PARPi are FDA approved for adjuvant treatment of locally advanced or metastatic breast cancer in patients with germline BRCA1/2 mutations, emerging data support their use as monotherapy in the neoadjuvant setting. Promising safety profiles of newer-generation PARPi further support this potential. However, resistance mechanisms specific to the neoadjuvant setting are poorly understood. To address this gap, we leveraged resources from a phase II neoadjuvant clinical trial (NCT03499353), analyzing tumors from patients with germline BRCA1/2 mutant breast tumors before and after six months of talazoparib monotherapy. Whole-transcriptome analyses were performed on these samples. Additionally, we established orthotopic patient-derived xenograft models from a subset of the patient tumors and conducted whole-exome and whole-transcriptome analysis. This integrative approach revealed both known and novel PARPi resistance mechanisms. In one case, overexpression of BRN2, encoding a transcription factor that plays a critical role in neurogenesis, led to activation of ATR/RAD51 and STAT3 pathways, restoring homologous recombination (HR) repair. BRN2-driven resistance could be reversed with ATR and STAT3 inhibitors, resensitizing cells to talazoparib. In another, an HR repair proficient tumor subclone lacking Shieldin 2 expression expanded during treatment and accounted for intrinsic resistance. Our findings highlight the need to determine intrinsic and anticipate acquired resistance pathways in treatment-naïve tumors and support combining PARPi with targeted agents to improve outcomes in the neoadjuvant setting.
2026-03-24 | GSE298644 | GEO
Project description:MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been previously reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. The pre-treatment sera of 42 stage II–III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs.
2013-07-20 | E-GEOD-49035 | biostudies-arrayexpress
Project description:BrighTNess was a phase III, multicenter, randomized, double-blind, placebo-controlled study that enrolled stage II/III TNBC patients to receive neoadjuvant chemotherapy with paclitaxel followed by doxorubicin/cyclophosphamid (AC), or the same plus carboplatin or carboplatin plus the PARP inhibitor veliparib concurrent with paclitaxel. Whole transcriptome RNA sequencing (RNAseq) was performed on pre-treatment research biopsies.
2021-01-08 | GSE164458 | GEO
Project description:Precision oncology research is challenging outside contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conducted a phosphoproteomic screening in a neoadjuvant trial of HER2-negative breast cancer patients (N=130) treated with paclitaxel or paclitaxel plus nintedanib, aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 15 candidate biomarkers through 2 independent patient sets (N=218) allowed finding a subgroup of patients characterized by high levels of CDK4 and Filamin-A, who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulated Filamin-A transcription, which in turn formed a complex with Tubulin and CLIP-170, what elicited increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allowed finding explainable predictive factors for paclitaxel.
2022-11-08 | PXD034355 | Pride
Project description:PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant TOP trial, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase IIα (TOP2A) and to develop a gene expression signature to identify those patients who do not benefit from anthracyclines. METHODS: The TOP trial included 149 patients, of which 141 were evaluable for response prediction analyses. The primary endpoint was pathological complete response (pCR). TOP2A and gene expression profiles were evaluated using pre-epirubicin biopsies. Gene expression data from ER-negative samples of the EORTC 10994/BIG 00-01 and MDACC 2003-0321 neoadjuvant trials were used for validation purposes. RESULTS: A pCR was obtained in 14% of the evaluable TOP patients. TOP2A amplification, but not protein overexpression, was significantly associated with pCR (p=0.001 and 0.22). We developed an “anthracycline-based score (A-Score)” that combines three signatures: a TOP2A gene signature and two previously published signatures related to tumor invasion and immune response. The A-Score was characterized by a high negative predictive value (NPV=0.98 [95% CI: 0.90-1.00]) overall, and in the HER2-negative and HER2-positive subpopulations. Its performance was independently confirmed in the anthracycline-based (FAC/FEC) arms of the two validation trials (BIG 00-01: 0.80 [0.61-0.92] and MDACC 2003-0321: 1.00 [0.80-1.00]). CONCLUSION: Given its high NPV, the A-Score could become, if further validated, a useful clinical tool to identify those patients who do not benefit from anthracyclines and could therefore be spared the non-negligible side effects.
2010-01-26 | GSE16446 | GEO
Project description:The limited benefit of immune checkpoint inhibitor in breast cancer indicates the pressing need to identify biomarkers of response to minimize risk and maximize benefit. In this study, we performed single cell RNA sequencing and T cell receptor sequencing on peripheral blood mononuclear cells to monitor the peripheral immune dynamics of an exploratory cohort of hormone receptor positive breast cancer patients treated with neoadjuvant nab-paclitaxel+pembrolizumab with the ultimate goal of identifying potential peripheral blood predictive biomarkers.
2025-07-09 | GSE300475 | GEO
Project description:Hypoxia protects cancer cells from chemotherapeutic drug-induced cell death. We used microarrays to detail the changes in gene expression underlying hypoxia-induced chemoresistance in cancer cells. MDA-MB-231 were exposed to paclitaxel or epirubicin under normoxia or hypoxia for 16hours, then RNA was extracted and analyzed by Affymetrix arrays
2012-07-02 | E-GEOD-39042 | biostudies-arrayexpress