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Updated: Jun 10, 2026
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Spatial transcriptomics in breast cancer reveals tumour microenvironment-driven drug responses and clonal therapeutic
María José Jiménez-Santos1, Santiago García-Martín1, Marcos Rubio-Fernández1,2
1Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Calle Melchor Fernández Almagro, 3, Madrid 28029, Spain.
Abstract:
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.
Insights
Understanding intratumour heterogeneity (ITH) in breast cancer is key. Our study reveals drug sensitivity varies by location within tumors and their microenvironment, guiding precision oncology.
Area of Science:
- Oncology
- Genomics
- Systems Biology
Background:
- Breast cancer treatment relies on subtypes, but precision oncology faces challenges due to intratumour heterogeneity (ITH).
- ITH, the presence of diverse malignant subpopulations with varying drug sensitivities within a single tumor, complicates treatment efficacy.
- The tumor microenvironment's role in treatment response is increasingly recognized, complementing the traditional tumor-centric view.
Purpose of the Study:
- To investigate the spatial distribution of drug sensitivity in breast cancer using spatial transcriptomics.
- To explore the influence of tumor microenvironment and spatial location on therapeutic response.
- To identify novel therapeutic targets and strategies for overcoming ITH.
Main Methods:
- Analysis of spatial transcriptomics data from breast cancer patient samples.
- Prediction of drug sensitivity across different tumor regions (core, interphase, microenvironment).
- Identification of ligand-receptor interactions driving distinct therapeutic clusters and functional differences.
Main Results:
- Observed diverse drug response patterns spatially, with a functional and sensitivity gradient from tumor core to periphery.
- Identified distinct therapeutic clusters associated with specific biological functions and ligand-receptor interactions.
- Found genetically identical subclones exhibiting differential drug responses based on their location within tumor ducts.
Conclusions:
- Tumor location and microenvironment composition are critical factors in predicting breast cancer drug sensitivity.
- Targeting ITH requires a comprehensive understanding of spatial biology and tumor-microenvironment interactions.
- Findings offer insights for optimizing precision oncology strategies and improving breast cancer treatment outcomes.
