PARP inhibitors in ovarian cancer: mechanisms of resistance and implications to therapy DOI Creative Commons

Sanat Kulkarni,

N. Seneviratne,

Çağla Tosun

и другие.

DNA repair, Год журнала: 2025, Номер unknown, С. 103830 - 103830

Опубликована: Апрель 1, 2025

Advanced epithelial ovarian cancer of the high-grade serous subtype (HGSOC) remains a significant clinical challenge due to development resistance current platinum-based chemotherapies. PARP1/2 inhibitors (PARPi) exploit well-characterised homologous recombination repair deficiency (HRD) in HGSOC and offer an effective targeted approach treatment. Several trials demonstrated that PARPi (olaparib, rucaparib, niraparib) significantly improved progression-free survival (PFS) recurrent maintenance setting. However, 40-70 % patients develop Resistance presenting ongoing clinic. Therefore, there is unmet need for novel therapies biomarkers identify intrinsic or acquired cancer. Understanding mechanisms crucial identifying molecular vulnerabilities, developing patient stratification guiding treatment decisions. Here, we summarise landscape associated with such as restored functionality, replication fork stability alterations PARP1 PARP2 DNA damage response. We highlight role circulating tumour (ctDNA) its potential 'real-time' Moreover, explore other innovative strategies aimed at overcoming specific mechanisms, including inhibition ATR, WEE1 POLQ. also examine rechallenge resistance.

Язык: Английский

PARP inhibitors in ovarian cancer: mechanisms of resistance and implications to therapy DOI Creative Commons

Sanat Kulkarni,

N. Seneviratne,

Çağla Tosun

и другие.

DNA repair, Год журнала: 2025, Номер unknown, С. 103830 - 103830

Опубликована: Апрель 1, 2025

Advanced epithelial ovarian cancer of the high-grade serous subtype (HGSOC) remains a significant clinical challenge due to development resistance current platinum-based chemotherapies. PARP1/2 inhibitors (PARPi) exploit well-characterised homologous recombination repair deficiency (HRD) in HGSOC and offer an effective targeted approach treatment. Several trials demonstrated that PARPi (olaparib, rucaparib, niraparib) significantly improved progression-free survival (PFS) recurrent maintenance setting. However, 40-70 % patients develop Resistance presenting ongoing clinic. Therefore, there is unmet need for novel therapies biomarkers identify intrinsic or acquired cancer. Understanding mechanisms crucial identifying molecular vulnerabilities, developing patient stratification guiding treatment decisions. Here, we summarise landscape associated with such as restored functionality, replication fork stability alterations PARP1 PARP2 DNA damage response. We highlight role circulating tumour (ctDNA) its potential 'real-time' Moreover, explore other innovative strategies aimed at overcoming specific mechanisms, including inhibition ATR, WEE1 POLQ. also examine rechallenge resistance.

Язык: Английский

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