Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA253668 | ENA |
REPOSITORIES: ENA
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Project description:We have witnessed the rise and fall of antiangiogenic therapy in breast cancer (BC). Nevertheless, clinical remissions were observed in patients and we were interested in studying the activity of antiangiogenic drugs in BC. Inefficacy of sunitinib was observed in mouse models of metastatic BC, where evidence of enhanced metastasis was reported, and lack of efficacy of sunitinib-docetaxel combination was recently reported in a phase III clinical trial. Our aim was to understand the mechanisms and predictors of response to sunitinib in BC in a cohort of patients with untreated locally advanced or operable BC treated with an upfront window of single agent sunitinib, followed by the combination of sunitinib and docetaxel. We have used microarray profiing to monitor the transcriptional changes associated with three distinct stages of treatment: at diagnosis and prior to any treatment (t1), after an upfront window of single agent sunitinib (t2) and after the combined treatment of sunitinib and docetaxel (t3). In addtion, this microarray data also allowed us to observe the transcriptional changes associated with primary resistance to angiogenic therapy in 4 of 12 patients likely mediated by an adaptive transcriptional response to hypoxia in these resistant tumors. In BC patients this is the first demonstration of primary resistance to antiangiogenic therapy.
2016-12-31 | GSE58837 | GEO
Project description:We established 3 types of primary xenograft models (KURC;Kyoto University Renal Cancer-1,2,3) derived from human renal cell carcinoma tissues, and 40 mg/day of sunitinib was orally administered. We performed microarray analysis to compare the gene expression profile of sunitinib-treated primary xenograft tumors (sensitive or resistant status) with that of vehicle-treated.
2015-03-10 | GSE66346 | GEO
Project description:Expression data from renal cancer xenograft tumor treated with sunitinib or vehicle
| PRJNA276577 | ENA
Project description:Transcriptome analysis was used to identify changes in human breast cancer cells (LM2-4) resistant to sunitinib (SuR) and after long term sunitinib withdrawal in vitro (LT-W for more than 6 months).
2018-11-22 | GSE122819 | GEO
Project description:We performed microarray analysis to compare the gene expression profile of sunitinib-treated primary xenograft tumors (sensitive or resistant status) with that of vehicle-treated.
2016-12-06 | GSE90896 | GEO
Project description:Although pre-clinical and clinical studies on PARP1 inhibitors, alone and in combination with DNA-damaging agents, show promising results, further ways to improve and broaden the scope of application of this therapeutic approach are warranted. To this end, we have investigated the possibility of improving the response of BRCA1 mutant breast cancer cells to PARP1 inhibition by co-targeting the PI3K pathway. The human breast cancer cell line MDA-MB-436, which lacks the expression of both BRCA1 and PTEN, was treated with the PARP1 inhibitor AG014699 as a single agent or in combination with the PI3K inhibitor LY294002 for 7 days. The human breast cancer cell line MDA-MB-436 was treated with the PARP1 inhibitor AG014699 as a single agent or in combination with the PI3K inhibitor LY294002 for 7 days. All treatments were performed in triplicates. Total RNA was extracted hybridized onto the Illumina HumanHT-12 v4.0 microarray platform.
2012-01-19 | E-GEOD-34817 | biostudies-arrayexpress
Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC). To explore ITH in detail, multiple tumor samples were taken from the primary renal tumors of mRCC patients who were sunitinib treated (n=23) or untreated (n=23). ITH of pathological grade, DNA (using array-based comparative genomic hybridisation), RNA (Illumina Beadarray) and protein (reverse phase protein array) were evaluated. Tumor grade heterogeneity was greater in treated compared to untreated tumors (P=0.002). Unsupervised and supervised analysis, for renal cancer driver, hypoxia and stromal gene signatures, was then performed. In untreated patient tumor samples, significant ITH occurred in chromosomal aberrations, RNA and protein expression, with clustering of DNA and RNA correlating for individual patients. In unsupervised analysis sunitinib therapy was not associated with increased ITH in DNA or RNA. However there was an increase in ITH for the driver mutation and hypoxia gene signatures (DNA and RNA) as well as increasing variability of protein expression with treatment (p<0.05). Despite this variability, significant chromosomal and RNA changes to targets of sunitinib, such as VHL, PBRM1 and CAIX, occurred in the treated samples. Together these findings suggest that sunitinib treatment has significant effects on the expression and ITH of key tumor and treatment specific genes. The results do not support the hypothesis that resistant clones are selected and predominate after initiation of targeted therapy; instead it appears that an initial clonal diversification occurs, supporting the hypothesis of polyclonal drug resistance.
2015-05-25 | GSE67818 | GEO
Project description:Gene expression data of HER2+ breast tumor samples Increasing evidence indicates that a subset of patients with HER2-positive breast cancer may achieve significant clinical benefit with anti-HER2 targeted therapy without chemotherapy. Thus, identification of biomarkers of long-term benefit from anti-HER2 agents is needed, especially in the metastatic setting. In the HERLAP study (NCT00842998), patients with HER2-positive metastatic breast cancer were randomized to trastuzumab or lapatinib as first-line therapy. Patients showing radiological signs of tumor regression after 8 weeks of treatment were allowed to continue on single agent anti-HER2 therapy until disease progression. Chemotherapy was added to anti-HER-2 therapy in patients failing to achieve tumor regression at the 8-week evaluation and those progressing at any time. Expression analysis of 105 selected genes was performed from formalin-fixed paraffin-embedded in 17 primary tumor samples. The research-based PAM50 intrinsic subtypes were also identified. The association of the expression of each biomarker with clinical outcome endpoints was evaluated. Nineteen patients were enrolled. In 4 patients (21.1%) we observed disease control lasting longer than 12 months with single agent anti-HER2 therapy (range 14.9-38.8 months). High expression of 17q12-21 amplicon genes HER2 and GRB7, and the PAM50 HER2-enriched intrinsic profile, were found significantly associated with 8-week overall response rate and with the duration of disease control during single agent anti-HER2 therapy. Conversely, high expression of luminal-related genes such as PGR, MDM2 or PIK3CA, or the PAM50 luminal intrinsic profile, was found associated with reduced benefit from single agent anti-HER2 therapy. Conclusions: Our data indicate that gene expression-based biomarkers can identify patients with HER2-positive metastatic breast cancer that benefit substantially from single agent chemo-free anti-HER2 targeted therapy. In the study presented here, a well-defined cohort of 21 breast cancer cases from the HERLAP trial, was used to acquire expression profiles of a total of 105 unique genes
2013-10-25 | E-GEOD-46350 | biostudies-arrayexpress
Project description:The diversity of human breast cancer subtypes has led to the hypothesis that breast cancer is a number of different diseases arising from cells at various stages of differentiation. We have derived clonal multipotent metastatic mammary cancer stem cells from the polyomavirus middle T mouse model of breast cancer, that can differentiate into luminal, myoepithelial and alveolar cells. When injected orthotopically at low-density, the resulting tumors express estrogen and progesterone receptors. With continued passage in vivo, the tumor cells undergo additional epigenetic and/or genetic changes that result in upregulation of Her2 expression or clonal expansion of cells that give rise to basal-like or claudin-low tumors. As in human tumors, the more aggressive tumor subtypes express nuclear p53. The temporal sequence of events suggests that contrary to current dogma, multiple tumor subtypes can originate from a single multipotent cancer stem cell that undergoes evolution during tumor progression. Furthermore, these data raise the possibility that a human polyomavirus may be a causative agent in spontaneous forms of human breast cancer. Three spontaneous PyVmT tumors and forty cell line derived tumors were analyzed. To generate cell line derived tumors, 10^6 tumor cells were injected orthotopically into four abdominal mammary fat pads in syngeneic C57Bl/6 female mice. After 6-8 weeks the mice were euthanized and the tumors excised and frozen at -80°C. One tumor per mouse 8-10mm in diameter was used for array analysis. RNA was extracted using the RNeasy kit (Qiagen) with on column DNA removal.
2014-09-12 | E-GEOD-61138 | biostudies-arrayexpress