The research in Strell’s group focuses on the biology of breast ductal carcinoma in situ (DCIS), with the overall ambition to comprehensively elucidate the underlying regulatory signaling mechanisms of early breast cancer evolution towards clinical disease progression and therapy response.
The research in Strell’s group focuses on the biology of breast ductal carcinoma in situ (DCIS), with the overall ambition to comprehensively elucidate the underlying regulatory signaling mechanisms of early breast cancer evolution towards clinical disease progression and therapy response. Special emphasis is placed to understand the interplay between genetic alterations and the tumor microenvironment by using state-of-the-art spatial mapping techniques for tissue analysis. Strell’s team further reaches beyond biological aspects and aims to uncover novel therapeutic opportunities as well as clinically relevant treatment stratification models for women with early breast cancer.
• EvoMaps – understanding the interplay of genetic alterations and the tumor microenvironment in DCIS
• DCIS immune architecture
• ImSignal – Mapping active immune cell signaling
Important results 2022
This project aims to adapt the in situ sequencing approach (Svedlund et al, EBioMedicine 2019; Lomakin et al, Nature 2022) to the Hyperion mass imaging system in order to enable a simultaneous mapping of genetic alterations and protein based cell typing and signaling pathway activation in diagnostic tissue sections. With this approach the group hopes to be able to identify the regulatory mechanisms beyond subclonal expansion in DCIS and how they relate to tumor progression and the development of radioresistant traits. This project is funded by the Trond Mohn Foundation.
DCIS immune architecture
The group has demonstrated previously that high level of tumor infiltrating lymphocytes (TILs) in DCIS are associated with worse prognosis (Schiza et al, EurJCancer 2022). During this work distinct TILs pattern were noted. Using imaging mass cytometry this project aims to uncover the cellular subtypes and signaling pathways within these distinct TILs pattern and how they are linked to clinical outcome and radiotherapy response.
A recently started project of the group, aiming to gather better insights into the resistance mechanisms towards immunotherapy in breast cancer. ImSignal intends to perform a highly multiplex mapping of active immune checkpoint signaling in tissue samples via the Hyperion mass imager.
Only few DCIS lesions have the potential to progress to invasive breast cancer. But since the regulatory mechanisms of cancer evolution are still largely undefined, a biological or clinical prediction of disease progression and therapy response remains difficult. The consequence is a high risk of over- as well as undertreatment for women with early breast cancer. Thus, improving guidance for clinicians and optimizing therapy applications is a major task for precision medicine.
Focus and plans for the next two years
The research team will prioritize the adaptation of their established spatial tissue profiling techniques to the Hyperion system. This will complement the ongoing spatial proteomics efforts at CCBIO with approaches for spatial genomics and signaling pathway mapping. The group will also seek contacts with CCBIO bioinformaticians and big data specialists to facilitate the integration of multiple layers with different spatial omics data into current bioinformatical analysis pipelines for deep tissue profiling.