ArticleBritish journal of cancer2022
BRCA mutations lead to XIAP overexpression and sensitise ovarian cancer to inhibitor of apoptosis (IAP) family inhibitors.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Regulated cell death in ovarian cancer: molecular mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Targeting MTPN sensitizes pancreatic cancer of wild-type BRCA1/2 to Cisplatin-based chemotherapy.Cancer gene therapy · 2025Article
- FRMD8 inhibits tumor metastasis in BRCA1-associated TNBC by negatively regulating tmTNF-α.Cellular & molecular biology letters · 2025Article
- E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance.Cell death discovery · 2025Article
- Observational
- Molecular Docking of Lactoferrin with Apoptosis-Related Proteins Insights into Its Anticancer Mechanism.International journal of molecular sciences · 2025Article
- Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.MedComm · 2024Review
- Prognostic value and therapeutic potential of IAP family in head and neck squamous cell carcinoma.Aging · 2024Article
- Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia.Journal of cellular and molecular medicine · 2023Article
- A signature based on anoikis-related genes for the evaluation of prognosis, immunoinfiltration, mutation, and therapeutic response in ovarian cancer.Frontiers in endocrinology · 2023Article
- Construction and Identification of an NLR-Associated Prognostic Signature Revealing the Heterogeneous Immune Response in Skin Cutaneous Melanoma.Clinical, cosmetic and investigational dermatology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe tested the hypothesis that inhibitor of apoptosis family (IAP) proteins may be altered in BRCA1-mutated ovarian cancers and that could affect the sensitivity to IAP inhibitors.
methodsThe levels of IAP proteins were evaluated in human cancers and cell lines. Cell lines were used to determine the effects of IAP inhibitors. The in vivo effects of treatments were evaluated in PDX mouse models.
resultsExpression of X-linked inhibitor of apoptosis (XIAP) is increased in BRCA1-mutated cancers and high levels are associated with improved patient outcomes after platinum chemotherapy. XIAP overexpression is mediated by NF-kB activation and is associated with an optimisation of PARP. BRCA1-mutated cell lines are particularly sensitive to IAP inhibitors due to an inhibitory effect on PARP. Both a BRCA1-mutated cell line with acquired resistance to PARP inhibitors and one with restored BRCA1 remain sensitive to IAP inhibitors. Treatment with IAP inhibitors restores the efficacy of PARP inhibition in these cell lines. The IAP inhibitor LCL161 alone and in combination with a PARP inhibitor, exhibited antitumour effects in PDX mouse models of resistant BRCA2 and 1-mutated ovarian cancer, respectively.
conclusionA clinical trial may be justified to further investigate the utility of IAP inhibitors.
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