Jiménez-Santos María José, García-Martín Santiago, Rubio-Fernández Marcos, Gómez-López Gonzalo, Al-Shahrour Fátima
Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Calle Melchor Fernández Almagro, 3, Madrid 28029, Spain.
Lung-H120 Group, Spanish National Cancer Research Centre (CNIO), Calle Melchor Fernández Almagro, 3, Madrid 28029, Spain.
NAR Cancer. 2024 Dec 18;6(4):zcae046. doi: 10.1093/narcan/zcae046. eCollection 2024 Dec.
Breast cancer patients are categorized into three subtypes with distinct treatment approaches. Precision oncology has increased patient outcomes by targeting the specific molecular alterations of tumours, yet challenges remain. Treatment failure persists due to the coexistence of several malignant subpopulations with different drug sensitivities within the same tumour, a phenomenon known as intratumour heterogeneity (ITH). This heterogeneity has been extensively studied from a tumour-centric view, but recent insights underscore the role of the tumour microenvironment in treatment response. Our research utilizes spatial transcriptomics data from breast cancer patients to predict drug sensitivity. We observe diverse response patterns across tumour, interphase and microenvironment regions, unveiling a sensitivity and functional gradient from the tumour core to the periphery. Moreover, we find tumour therapeutic clusters with different drug responses associated with distinct biological functions driven by unique ligand-receptor interactions. Importantly, we identify genetically identical subclones with different responses depending on their location within the tumour ducts. This research underscores the significance of considering the distance from the tumour core and microenvironment composition when identifying suitable treatments to target ITH. Our findings provide critical insights into optimizing therapeutic strategies, highlighting the necessity of a comprehensive understanding of tumour biology for effective cancer treatment.
乳腺癌患者被分为三种具有不同治疗方法的亚型。精准肿瘤学通过针对肿瘤的特定分子改变提高了患者的治疗效果，但挑战依然存在。由于同一肿瘤内存在几种具有不同药物敏感性的恶性亚群，即肿瘤内异质性（ITH），治疗失败的情况仍然存在。这种异质性已从以肿瘤为中心的角度进行了广泛研究，但最近的见解强调了肿瘤微环境在治疗反应中的作用。我们的研究利用乳腺癌患者的空间转录组学数据来预测药物敏感性。我们观察到肿瘤、间期和微环境区域的不同反应模式，揭示了从肿瘤核心到周边的敏感性和功能梯度。此外，我们发现具有不同药物反应的肿瘤治疗簇与由独特的配体-受体相互作用驱动的不同生物学功能相关。重要的是，我们确定了基因相同的亚克隆，它们根据在肿瘤导管内的位置而有不同的反应。这项研究强调了在确定针对ITH的合适治疗方法时考虑与肿瘤核心的距离和微环境组成的重要性。我们的发现为优化治疗策略提供了关键见解，突出了全面了解肿瘤生物学以有效治疗癌症的必要性。
