个性化肿瘤学是癌症研究的前沿。个性化肿瘤学的目标是选择性地杀死癌细胞并尽量减少对正常组织的副作用。这可以通过识别和针对癌细胞易感性的方式来实现，这种方式与正常细胞不同。许多癌症缺乏高保真度的DNA修复途径来维持基因组稳定性，如同源重组（HR）。这种癌症对诱导DNA损伤或抑制DNA修复途径的靶向治疗非常敏感。个性化肿瘤学的一个显著例子和一个标志性的案例是PARP1/2抑制剂（PARPi），它们通过防止DNA间隙或单链断裂（SSB）的修复而选择性地杀死HR缺陷（HRD）癌细胞（Slade，2020）。细胞周期检查点的抑制剂，如CHK1和WEE1，也可以通过推动癌细胞经过细胞周期，尽管未修复的DNA损伤，并通过有丝分裂灾难引起死亡，从而消除HRD癌症（Groelly et al，2022）。PARPi已被批准用于卵巢癌，乳腺癌，胰腺癌和前列腺癌的治疗，但其他具有HRD特征（HRDness）的癌症类型也可能对PARPi治疗产生反应。 Planas-Paz等（2023）现在表明许多肉瘤表现出HRDness并对PARP1/2和WEE1抑制剂产生反应，因此为治疗难治性癌症提供了一种新的个性化肿瘤学方法。©2023年作者。根据CC BY 4.0许可证的条款发布。

Personalised oncology is at the forefront of cancer research. The goal of personalised oncology is to selectively kill cancer cells while minimising side effects on normal tissue. This can be achieved by identifying and targeting cancer vulnerabilities that distinguish it from normal cells. Many cancers are deficient in high-fidelity DNA repair pathways that maintain genomic stability, such as homologous recombination (HR). Such cancers are highly sensitive to targeted therapies that induce DNA damage or inhibit DNA repair pathways. A notable example and a poster child of personalised oncology are PARP1/2 inhibitors (PARPi) that selectively kill HR-deficient (HRD) cancer cells by preventing repair of DNA gaps or single-strand breaks (SSBs) (Slade, 2020). Inhibitors of cell cycle checkpoints such as CHK1 and WEE1 can also eliminate HRD cancers by pushing cancer cells through the cell cycle despite unrepaired DNA damage and causing death by mitotic catastrophe (Groelly et al, 2022). PARPi have been approved for the treatment of ovarian, breast, pancreatic, and prostate cancer but other cancer types with an HRD signature (HRDness) may also respond to PARPi treatment. Planas-Paz et al (2023) now show that many sarcomas show HRDness and respond to PARP1/2 and WEE1 inhibitors, thus offering a new personalised oncology approach for this treatment-refractory cancer.© 2023 The Authors. Published under the terms of the CC BY 4.0 license.