Similar Datasets
Project description:Identification of PARPi sensitive transcripts in prostate cancer
| PRJNA484893 | ENA
Project description:Evaluation of the genome wide impact of cell cycle position on DHT stimulated gene expression programs. Results show differential cell cycle regulated gene expression in different cell cycle phases.
2016-10-05 | GSE82201 | GEO
Project description:We have previously established an in vitro model of PARPi-resistant ovarian cancer by long-term exposure of UWB1.289 ovarian cancer cells (and their isogenic derivatives UWB1.289+BRCA1) to incrementally ascending olaparib concentrations. After finalizing this model, we performed RNA-seq, in order to identify differentially expressed transcript in the PARPi-resistant cells, with a focus on genes related to DNA-repair, multi-drug resistance and EMT. As a result, we show that the phenotype of PARPi resistance is associated with EMT-like traits and up-regulation of selective multi-drug related transcripts.
2023-07-31 | GSE235980 | GEO
Project description:Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPi) are approved to treat recurrent ovarian cancer with BRCA1 or BRCA2 mutations, and as maintenance therapy for recurrent platinum sensitive ovarian cancer (BRCA wild-type or mutated) after treatment with platinum. However, the acquired resistance against PARPi remains a clinical hurdle. Our previous study has demonstrated that PARPi can enhance the Aldehyde dehydrogenase (ALDH) activity in ovarian cancer cells, mainly through inducing expression of ALDH1A1, an isoform of the ALDH family. In addition, an ALDH1A1 selective inhibitor can synergize with olaparib in killing EOC cells carrying BRCA2 mutation in both in vitro cell culture and the in vivo xenograft animal model. In order to elucidating the mechanism by which ALDH1A1 renders PARPi resistance to ovarian cancer, we performed RNA-seq analysis to identify genes whose expression can be regulated by ALDH1A1.
2023-07-19 | GSE226018 | GEO
Project description:Leukaemic blasts share common pathological features with other cancers including genome instability and impaired DNA damage response and repair (DDR). The limited efficacy of DDR inhibitors, such as poly (ADP-ribose) polymerase inhibitors (PARPi) as single agents in acute myeloid leukaemia (AML) is partly owing to activation of alternative DDR pathways and cytotoxicity to healthy tissues. Their strengths may lie in combination strategies targeting other essential proteins required for leukaemogenesis. We have identified the histone demethylase, KDM4A, as a critical epigenetic regulator required for AML cell survival. Depletion of KDM4A causes aberrant DDR pathway activation and subsequent DNA damage. We hypothesised that KDM4A inhibitors (KDM4Ai) increase AML cell reliance on specific DDR pathways for survival and may sensitise them to PARPi. We aimed to analyse transcriptional profiling (RNA Seq) changes associated with varying concentrations of KDM4A inhibition in monotherapy and as a combination therapy with a single PARPi treatment following 36hrs treatment. In summary, our study identifies a novel potential therapeutic strategy for AML. KDM4Ai sensitises cells to PARPi through impairing further NHEJ repair and enhancing PARP trapping leading to selective leukaemic cell death. These results warrant future clinical evaluation of this promising combination strategy in AML and other cancers.
2022-12-31 | GSE164437 | GEO
Project description:Cancer-associated fibroblasts (CAFs) play significant roles in drug resistance through different ways. Antitumor therapies, including molecular targeted interventions, not only effect tumor cells but also modulate the phenotype and characteristics of CAFs, which can in turn blunt the therapeutic response. Little is known about how stromal fibroblasts respond to poly (ADP-ribose) polymerase inhibitors (PARPis) in ovarian cancer (OC) and subsequent effects on tumor cells. This is a study to evaluate how CAFs react to PARPis and their potential influence on PARPi resistance in OC. We discovered that OC stromal fibroblasts exhibited intrinsic resistance to PARPis and were further activated after the administration of PARPis. PARPi-challenged fibroblasts displayed a specific secretory profile characterized by increased secretion of CCL5, MIP-3α, MCP3, CCL11, and ENA-78. Mechanistically, increased secretion of CCL5 through activation of the NF-κB signaling pathway was required for PARPi-induced stromal fibroblast activation in an autocrine manner. Moreover, neutralizing CCL5 partly reversed PARPi-induced fibroblast activation and boosted the tumor inhibitory effect of PARPis in both BRCA1/2-mutant and BRCA1/2-wild type xenograft models. Our study revealed that PARPis could maintain and improve stromal fibroblast activation involving CCL5 autocrine upregulation. Targeting CCL5 might offer a new treatment modality in overcoming the reality of PARPi resistance in OC.
2021-06-05 | GSE164088 | GEO
Project description:RNA-Seq of PARPi-resistant ovarian cancer cells
| PRJNA988124 | ENA
Project description:Role of ALDH1A1 in PARPi resistance in ovarian cancer
| PRJNA938376 | ENA
Project description:The objective of this study was to describe the treatment experience of patients with recurrent epithelial ovarian cancer who are retreated with an inhibitor of poly(ADP-ribose)-polymerase (PARPi). We conducted a multi-institutional, retrospective review of ovarian cancer patients who received ?2 lines of therapy containing a PARPi. Demographic, clinical, and pathological data were analyzed with descriptive statistics. Twenty-two patients were identified. For initial PARPi (PARPi1), 12 patients (54.5%) received veliparib, 7 (31.8%) olaparib and 3 (13.6%) rucaparib resulting in 10 patients who had no evidence of disease at the completion of therapy (NED), 3 partial responses (PR), 4 stable disease (SD), and 3 progressive disease (PD). (All 10 CRs involved veliparib given in conjunction with cytotoxic chemotherapy). PARPi1 was used as maintenance in 2 patients. PARPi1 was discontinued because planned number of cycles was reached (n = 10), progression (n = 8), toxicity (n = 2), other (n = 2). For second PARPi (PARPi2), 10 patients (45.4%) received niraparib, 6 (27.3%) olaparib, and 6 (27.3%) rucaparib resulting in 3 PR, 13 SD, and 3 PD. PARPi2 was used as maintenance in 3 patients. The 3 patients who experienced a PR to PARPi2 had a BRCA mutation and were NED following PARPi1. PARPi2 was discontinued because of progression (n = 13), toxicity (n = 6), other (n = 2). One patient currently remains on PARPi2. Toxicity after PARPi1 was not associated with toxicity from PARPi2 (p > 0.05). With 3 approved PARPi for different indications including frontline and recurrence, the opportunity to reuse PARPi has increased. Characterizing those who should be re-challenged is an important initiative moving forward.
| S-EPMC7840844 | biostudies-literature
Project description:PARPi resistance screening in KB2P-3.4 2D cell lines
| PRJEB74933 | ENA