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PARP抑制剂在乳腺癌和妇科癌症中的耐药性：耐药机制与联合治疗策略。

PARP inhibitor resistance in breast and gynecological cancer: Resistance mechanisms and combination therapy strategies.

作者信息

Wang Nannan, Yang Yan, Jin Dongdong, Zhang Zhenan, Shen Ke, Yang Jing, Chen Huanhuan, Zhao Xinyue, Yang Li, Lu Huaiwu

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

出版信息

Front Pharmacol. 2022 Aug 25;13:967633. doi: 10.3389/fphar.2022.967633. eCollection 2022.

DOI:10.3389/fphar.2022.967633
PMID:36091750
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9455597/
Abstract

Breast cancer and gynecological tumors seriously endanger women's physical and mental health, fertility, and quality of life. Due to standardized surgical treatment, chemotherapy, and radiotherapy, the prognosis and overall survival of cancer patients have improved compared to earlier, but the management of advanced disease still faces great challenges. Recently, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) have been clinically approved for breast and gynecological cancer patients, significantly improving their quality of life, especially of patients with BRCA1/2 mutations. However, drug resistance faced by PARPi therapy has hindered its clinical promotion. Therefore, developing new drug strategies to resensitize cancers affecting women to PARPi therapy is the direction of our future research. Currently, the effects of PARPi in combination with other drugs to overcome drug resistance are being studied. In this article, we review the mechanisms of PARPi resistance and summarize the current combination of clinical trials that can improve its resistance, with a view to identify the best clinical treatment to save the lives of patients.

摘要

乳腺癌和妇科肿瘤严重危及女性的身心健康、生育能力和生活质量。由于标准化的手术治疗、化疗和放疗，与早期相比，癌症患者的预后和总生存率有所改善，但晚期疾病的治疗仍面临巨大挑战。最近，聚（ADP - 核糖）聚合酶（PARP）抑制剂（PARPis）已在临床上被批准用于乳腺癌和妇科癌症患者，显著提高了他们的生活质量，尤其是对于携带BRCA1/2突变的患者。然而，PARPi治疗面临的耐药性阻碍了其临床推广。因此，开发新的药物策略使影响女性的癌症对PARPi治疗重新敏感是我们未来研究的方向。目前，正在研究PARPi与其他药物联合使用以克服耐药性的效果。在本文中，我们回顾了PARPi耐药的机制，并总结了目前可改善其耐药性的联合临床试验情况，以期确定挽救患者生命的最佳临床治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/60079f1e7592/fphar-13-967633-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/bea340e760ce/fphar-13-967633-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/8311fd3d2085/fphar-13-967633-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/ccb589f1a158/fphar-13-967633-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/e570e0fcd785/fphar-13-967633-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/60079f1e7592/fphar-13-967633-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/bea340e760ce/fphar-13-967633-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/8311fd3d2085/fphar-13-967633-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/ccb589f1a158/fphar-13-967633-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/e570e0fcd785/fphar-13-967633-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/9455597/60079f1e7592/fphar-13-967633-g005.jpg

相似文献

[1]
PARP inhibitor resistance in breast and gynecological cancer: Resistance mechanisms and combination therapy strategies.

Front Pharmacol. 2022-8-25

[2]
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[3]
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Clin Cancer Res. 2018-4-3

[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Treatment of ovarian cancer: From the past to the new era (Review).

Oncol Lett. 2025-6-3

[2]
Controversies and clinical unknowns in the use of PARP inhibitors in ovarian cancer.

Ther Adv Med Oncol. 2025-6-14

[3]
and Beyond: Impact on Therapeutic Choices Across Cancer.

Cancers (Basel). 2024-12-24

[4]
Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a mutation.

Oncol Lett. 2024-11-20

[5]
BRCA-mutated breast cancer: the unmet need, challenges and therapeutic benefits of genetic testing.

Br J Cancer. 2024-11

[6]
Poly (ADP-ribose) polymerase inhibitor therapy and mechanisms of resistance in epithelial ovarian cancer.

Front Oncol. 2024-7-29

[7]
[F]F-Poly(ADP-Ribose) Polymerase Inhibitor Radiotracers for Imaging PARP Expression and Their Potential Clinical Applications in Oncology.

J Clin Med. 2024-6-11

[8]
Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors.

Cells. 2024-5-17

[9]
Drug resistance in ovarian cancer: from mechanism to clinical trial.

Mol Cancer. 2024-3-28

[10]
Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy.

Front Pharmacol. 2024-1-24

本文引用的文献

[1]
Endometrial cancer.

Lancet. 2022-4-9

[2]
BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1.

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Recurrent Endometrial Cancer: Local and Systemic Treatment Options.

Cancers (Basel). 2021-12-14

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Br J Cancer. 2022-4

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Repurposing Ceritinib Induces DNA Damage and Enhances PARP Inhibitor Responses in High-Grade Serous Ovarian Carcinoma.

Cancer Res. 2022-1-15

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J Transl Med. 2021-10-7

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