ArticleScientific reports2018
DEBIO 1143, an IAP inhibitor, reverses carboplatin resistance in ovarian cancer cells and triggers apoptotic or necroptotic cell death.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- The SMAC-mimetic xevinapant differentially enhances cisplatin and immune checkpoint blockade efficacy in high-risk HPV-positive tumors.Translational oncology · 2026Article
- ZNF468 stabilization by RNF4 enhances apoptosis resistance and carboplatin resistance in breast cancer via transcription activation of XIAP.Genes & genomics · 2026Article
- Comparative efficacy of melatonin and glutathione in mitigating carboplatin-induced ovarian toxicity in rats.Clinics (Sao Paulo, Brazil) · 2026Article
- Establishment of a Prognostic Necroptosis-Related lncRNA Signature in Ovarian Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer.Cancer research communications · 2025Article
- The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development.Apoptosis : an international journal on programmed cell death · 2025Review
- Mechanisms of apoptosis-related non-coding RNAs in ovarian cancer: a narrative review.Apoptosis : an international journal on programmed cell death · 2025Review
- PI3Kα-specific inhibitor BYL-719 synergizes with cisplatin in vitro in PIK3CA-mutated ovarian cancer cells.Scientific reports · 2025Article
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- Xevinapant plus avelumab in advanced solid tumours, with a dose expansion in advanced non-small-cell lung cancer: exploratory biomarker, safety and efficacy analyses from an open-label, nonrandomised phase Ib study.Therapeutic advances in medical oncology · 2025Article
- Physician Perspectives on the Management of Patients with Resected High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck Who Are Ineligible to Receive Cisplatin: A Podcast.Targeted oncology · 2024Article
- NK cell line modified to express a potent, DR5 specific variant of TRAIL, show enhanced cytotoxicity in ovarian cancer models.Heliyon · 2024Article
- Article
- Inhibiting the inhibitors: Development of the IAP inhibitor xevinapant for the treatment of locally advanced squamous cell carcinoma of the head and neck.Cancer treatment reviews · 2023Review
- A comprehensive pan-cancer analysis of necroptosis molecules in four gynecologic cancers.BMC cancer · 2022Article
- IAP antagonist GDC-0917 is more potent than Debio1143 in promoting cell death, c-IAP1 degradation and tumor growth inhibition.Cell death & disease · 2022Article
- Inferences of carboplatin response-related signature by integrating multiomics data in ovarian serous cystadenocarcinoma.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Functional Genomic Identification of Predictors of Sensitivity and Mechanisms of Resistance to Multivalent Second-Generation TRAIL-R2 Agonists.Molecular cancer therapeutics · 2022Article
- Potential for reversingMolecular therapy oncolytics · 2022Article
- The targeted SMAC mimetic SW IV-134 augments platinum-based chemotherapy in pre-clinical models of ovarian cancer.BMC cancer · 2022Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The poor prognosis of ovarian cancer (it is the leading cause of death from gynecological cancers) is mainly due to the acquisition of resistance to carboplatin. Among the possible resistance pathways, resistance to apoptosis and especially the overexpression of inhibitor of apoptosis proteins (IAP) cIAP1 and X-linked IAP (XIAP), have been implicated. DEBIO 1143, a SMAC (second mitochondria-derived activator of caspase) mimetic, belongs to a new class of targeted agents currently being evaluated in clinical trials, which activate apoptotic cell death and block pro-survival signaling in cancer cells. Here, we demonstrate that DEBIO 1143 in vitro inhibits the cell viability of two carboplatin-sensitive cell lines (IGROV-1 and A2780S) as well as three carboplatin-resistant cell lines (A2780R, SKOV-3 and EFO-21). Of note, DEBIO 1143 is able to reverse resistance to carboplatin by inducing cell death either by apoptosis or necroptosis depending on the cell lines. To identify a biomarker able to predict the sensitivity of the cell lines to DEBIO 1143 treatment we analyzed the expression of the DEBIO 1143 targets cIAP1 and XIAP, and one of their downstream targets, caspase 9. These proteins did not constitute a marker of DEBIO 1143 sensitivity/resistance. Importantly, we confirmed these findings in vivo in SKOV-3 xenograft models where DEBIO 1143 highly potentiated carboplatin treatment.
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