多聚ADP核糖聚合酶抑制剂(PARPi)
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华中科技大学发表最新Science子刊论文
生物世界· 2025-08-19 08:00
Core Viewpoint - The study highlights the effectiveness of sequential treatment with PARP inhibitors (PARPi) followed by WEE1 inhibitors (WEE1i) in enhancing antitumor immune responses in ovarian cancer models, compared to single or combined therapies [3][4][6][7]. Group 1: Treatment Efficacy - Sequential treatment with PARPi followed by WEE1i is more effective in eradicating cancer and inducing stronger antitumor immune responses than monotherapy or combination therapy [4][6]. - Both sequential and simultaneous treatment regimens induce lethal DNA damage in cancer cells and activate the cGAS-STING pathway, but sequential treatment results in higher T cell survival rates [6][7]. Group 2: Mechanism of Action - PARP is a multifunctional enzyme that acts as a sensor for DNA damage and plays a crucial role in DNA repair [6]. - The study found that T cells recover from DNA damage faster than cancer cells after DDRi treatment, indicating a potential advantage for sequential therapy [6][7]. Group 3: Clinical Implications - In preclinical models of high-grade serous ovarian cancer and treatment-resistant ovarian cancer, the combination of immune checkpoint inhibitors and CAR-T cell therapy with sequential treatment is more effective than monotherapy [6].