ArticleOncotarget2015
Loss of INPP4B causes a DNA repair defect through loss of BRCA1, ATM and ATR and can be targeted with PARP inhibitor treatment.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.Cell death & disease · 2022Pooled it
- Study of inborn errors of immunity associated lymphoid proliferations identifies association of presence of somatic variations with large cell morphology, copy number alterations in TNFAIP3 and heterozygous variants in EMSY.Virchows Archiv : an international journal of pathology · 2026Article
- Upregulation of miR-151a-5p in high DFI sperm induces DNA damage and mitochondrial dysfunction by targeting INPP4B and VAMP1.Reproductive biology and endocrinology : RB&E · 2025Article
- Role of inositol polyphosphate-4-phosphatase type II in oncogenesis of digestive system tumors.World journal of gastrointestinal oncology · 2023Review
- Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer.Acta pharmacologica Sinica · 2021Review
- Article
- The INPP4B Tumor Suppressor Modulates EGFR Trafficking and Promotes Triple-Negative Breast Cancer.Cancer discovery · 2020Article
- Investigating the duality ofOncotarget · 2019Article
- PI3K-AKT-mTOR and NFκB Pathways in Ovarian Cancer: Implications for Targeted Therapeutics.Cancers · 2019Review
- Dancing with the DNA damage response: next-generation anti-cancer therapeutic strategies.Therapeutic advances in medical oncology · 2018Review
- Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas.The Journal of pathology · 2017Article
- Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases.PLoS medicine · 2016Article
- INPP4B-mediated DNA repair pathway confers resistance to chemotherapy in acute myeloid leukemia.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Role of Biomarkers in the Development of PARP Inhibitors.Biomarkers in cancer · 2016Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Treatment options for ovarian cancer patients remain limited and overall survival is less than 50% despite recent clinical advances. The lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described as a tumor suppressor in the PI3K/Akt pathway with loss of expression found most pronounced in breast, ovarian cancer and melanoma. Using microarray technology we identified a DNA repair defect in INPP4B-deficient cells, which we further characterized by comet assays and quantification of γH2AX, RAD51 and 53BP1 foci formation. INPP4B loss resulted in significantly increased sensitivity towards PARP inhibition, comparable to loss of BRCA1 in two- and three-dimensional in vitro models, as well as in in vivo xenograft models. Mechanistically, we discovered that INPP4B forms a protein complex with the key players of DNA repair, ATR and BRCA1, in GST pulldown and 293T overexpression assays, and INPP4B loss affects BRCA1, ATM and ATR protein stability resulting in the observed DNA repair defect. Given that INPP4B loss has been found in 40% of ovarian cancer patients, this study provides the rationale for establishing INPP4B as a biomarker of PARP inhibitor response, and consequently offers novel therapeutic options for a significant subset of patients. Loss of the tumor suppressor inositol polyphosphate 4-phosphatase type II (INPP4B) results in a DNA repair defect due to concomitant loss of BRCA1, ATR and ATM and can be therapeutically targeted with PARP inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.