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olaparib (myChoice CDx)

✓ Approved

Myriad Genetics, Inc. · 辅助诊断 · 辅助诊断

什么是 olaparib？

olaparib 是一种辅助诊断，由Myriad Genetics, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Others。

药物档案

商品名myChoice CDx
公司Myriad Genetics, Inc.
药物类别辅助诊断
给药途径Others
状态Approved
来源： ClinicalTrials.gov, Myriad Genetics, Inc.

治疗适应症

olaparib 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Uterine cancer✓ Approved

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Endometrial cancer (EC) incidence continues to rise, underscoring the need for effective therapies beyond BRCA-mutant disease. Although PTEN loss, a frequent alteration in EC, has been implicated in impaired homologous recombination and increased sensitivity to PARP inhibitors, responses to PARP inhibitor monotherapy remain variable and are often limited by resistance mechanisms in PTEN-deficient tumours. Here, we show that the dual PARP/tankyrase (TNKS) inhibitor JPI-547 exerts potent antitumor activity, particularly in PTEN-deficient Ishikawa tumours. In vitro, JPI-547 and olaparib more effectively reduced cell survival in PTEN-deficient cells, and combined treatment with olaparib and the TNKS inhibitor XAV-939 induced synergistic cytotoxicity with elevated DNA double-strand breaks. Dual PARP/TNKS inhibition did not further suppress RAD51 but modulated non-homologous end joining and attenuated Wnt/β-catenin signalling in a PTEN-dependent manner. PTEN knockdown further showed enhanced vulnerability to combined targeting. These findings show that JPI-547 enhances antitumor efficacy in PTEN-deficient EC by disrupting DNA repair pathways and Wnt signalling, supporting dual PARP/TNKS inhibition as a potential therapeutic strategy and providing a rationale for further clinical evaluation.

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