2023
DOI: 10.1101/2023.01.18.524417
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Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma

Abstract: Ovarian high-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer with limited therapeutic options. In recent years, PARP inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Therapies disrupting the spliceosome alter cancer transcriptomes and have shown potential to improve PARP inhibitor response. Indisulam (E7070) has been identified as a molecular glue t… Show more

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Cited by 2 publications
(3 citation statements)
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“…A recent study demonstrated that the loss of RBM39 induces splicing defects in key DNA damage repair genes, such as ATM and BRCA1, in ovarian cancer, leading to increased sensitivity to cisplatin and various PARPi 18 . Although this study is similar to ours, a few important contexts are different.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…A recent study demonstrated that the loss of RBM39 induces splicing defects in key DNA damage repair genes, such as ATM and BRCA1, in ovarian cancer, leading to increased sensitivity to cisplatin and various PARPi 18 . Although this study is similar to ours, a few important contexts are different.…”
Section: Discussionmentioning
confidence: 99%
“…A recent report by Xu Y. et al indicated that E7820 affects the RNA splicing of some HRR genes but did not demonstrate that HRD can serve as a biomarker for predicting E7820 response 18 . Since our initial screening in the PDX models showed marked shrinkage of the tumors with HRD, we hypothesized that growth suppression may become dominant after longterm exposure to the compound.…”
Section: Cell Growth Inhibition Becomes Apparent Under Long-term Trea...mentioning
confidence: 96%
“…Recently, poly-ADP ribose polymerase inhibitors (PARPi) have demonstrated efficacy in patients with deficient homologous recombination (HR). Unfortunately, PARPi are less effective in cancers with proficient HR (~50% of patients); moreover, acquired drug resistance and relapse remains a clinical problem 2 . Therefore, new therapeutic approaches are required.…”
Section: Introductionmentioning
confidence: 99%