英国Tailor Bio有限公司Geoff Macintyre研究组取得一项新突破。他们的研究认为利用染色体不稳定性特征预测化疗耐药性。该研究于2025年6月23日发表于国际一流学术期刊《自然—遗传学》杂志上。

在这里，该课题组人员提出了染色体不稳定性标记生物标志物，识别对铂，紫杉烷和蒽环类药物治疗的耐药性，主题为单一基因组测试。在以真实世界队列为主题的回顾性模拟随机对照生物标志物临床试验（n = 840）中，预测耐药患者卵巢癌紫杉烷（风险比（HR）为7.44）和蒽环类药物（风险比为1.88），转移性乳腺紫杉烷（风险比为3.98）和蒽环类药物（风险比为3.69）的治疗失败风险升高，转移性前列腺紫杉烷（风险比为5.46）。非随机模拟显示卵巢铂耐药（HR为1.46）和肉瘤蒽环类药物耐药（HR为3.59）的预测能力。课题组论证了全基因组测序、捕获面板测序和无细胞DNA的可行性。他们的发现强调了染色体不稳定性特征在预测多种癌症对化疗的耐药性方面的临床价值，并有可能将一刀切的化疗方法转变为精确的、量身定制的治疗。

研究人员表示，化疗通常没有精确的生物标志物，使患者暴露于毒副作用，而没有保证的益处。

附：英文原文

Title: Predicting resistance to chemotherapy using chromosomal instability signatures

Author: Thompson, Joe Sneath, Madrid, Laura, Hernando, Barbara, Sauer, Carolin M., Vias, Maria, Escobar-Rey, Maria, Leung, Wing-Kit, Garcia-Lopez, Diego, Huckstep, Jamie, Sekowska, Magdalena, Hosking, Karen, Jimenez-Linan, Mercedes, Reinius, Marika A. V., Roy, Abhipsa, Abdulle, Omar, Pangonyte, Justina, Dobson, Harry, Cullen, Amy E., De Silva, Dilrini, Gmez-Snchez, David, Torres, Marina, Fernndez-Sanromn, ngel, Sanders, Deborah, Martins, Filipe Correia, Funingana, Ionut-Gabriel, Codacci-Pisanelli, Giovanni, Quintela-Fandino, Miguel, Markowetz, Florian, Yip, Jason, Brenton, James D., Piskorz, Anna M., Macintyre, Geoff

Issue&Volume: 2025-06-23

Abstract: Chemotherapies are often given without precision biomarkers, exposing patients to toxic side effects without guaranteed benefit. Here we present chromosomal instability signature biomarkers that identify resistance to platinum-, taxane- and anthracycline-based treatments using a single genomic test. In retrospectively emulated randomized-control biomarker clinical trials using real-world cohorts (n=840), predicted resistant patients had elevated treatment failure risk for taxane (hazard ratio (HR) of 7.44) and anthracycline (HR of 1.88) in ovarian, taxane (HR of 3.98) and anthracycline (HR of 3.69) in metastatic breast and taxane (HR of 5.46) in metastatic prostate. Nonrandomized emulations showed predictive capacity for platinum resistance in ovarian (HR of 1.46) and anthracycline in sarcoma (HR of 3.59). We demonstrate feasibility using whole-genome sequencing, capture-panel sequencing and cell-free DNA. Our findings highlight the clinical value of chromosomal instability signatures in predicting resistance to chemotherapies across multiple cancer types, with the potential to transform the one-size-fits-all chemotherapy approach into precise, tailored treatment.

DOI: 10.1038/s41588-025-02233-y

Source: https://www.nature.com/articles/s41588-025-02233-y