The Landscape of PARP Inhibitors in Solid Cancers

OncoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 18, P. 297 - 317

Published: March 1, 2025

PARP inhibitors are a class of agents that have shown significant preclinical activity in models defective homologous recombination (HR). The identification synthetic lethality between HR defects and inhibition led to several clinical trials tumors with known (initially mutations BRCA1/2 genes subsequently other involved HR). These studies demonstrated responses breast ovarian cancers, which proportion patients defects. Since the approval first inhibitor (PARPi), olaparib, been developed, expanding armamentarium available clinicians this setting. positive results obtained cancer expanded use PARPi solid defects, including prostate pancreatic these identified. now also for subset This review summarizes their potential when combined agents, immune checkpoint likely further increase survival still needs dramatic improvement.

Language: Английский

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

DNA repair, Journal Year: 2025, Volume and Issue: unknown, P. 103830 - 103830

Published: April 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.

Language: Английский

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Shedding LIGHT on the changing landscape of poly‐ADP ribose polymerase inhibitors in ovarian cancer

Cancer, Journal Year: 2025, Volume and Issue: 131(8)

Published: April 7, 2025

The landscape of poly‐ADP ribose polymerase (PARP) inhibitor use in ovarian cancer has evolved since the LIGHT study was designed. However, this still provides valuable insight into biomarkers PARP activity and association with overall survival.

Language: Английский

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Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer

Current Oncology, Journal Year: 2024, Volume and Issue: 31(12), P. 8023 - 8038

Published: Dec. 18, 2024

Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian remains challenging. Diverse tumour biology and extensive heterogeneity can limit the translatability of genetic profiling contribute to a lack biomarkers treatment response. This review addresses barriers precision for cancer, including obtaining adequate representative tissue samples analysis, developing functional standardised screening methods, navigating data infrastructure management. Ethical concerns related patient consent, privacy health equity are also explored. We highlight socio-economic complexities propose strategies overcome these challenges with an emphasis on accessibility education amongst patients professionals development regulatory frameworks support clinical integration. Interdisciplinary collaboration is essential drive progress improve disease management outcomes.

Language: Английский

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Homologous recombination deficiency (HRD) diagnostics: underlying mechanisms and new perspectives

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 44(1)

Published: Dec. 26, 2024

Language: Английский

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