Cancer is an enormous biomedical challenge, in part due to the complexity of cancer cell dynamics. The combination of intrinsic genetic alterations and cues from the tumour microenvironment impacts the cancer phenotype and creates heterogeneous tumours that evolve in space and time. Cancer cells develop distinct phenotypes in diverse tumour regions and different metastatic locations. In addition, cancer progression, metastatic dissemination, and development of therapeutic resistance affect cellular interactions over time. Therefore, understanding tumour dynamics is critical for developing novel therapeutic approaches. Changes in protein expression are central determinants of cancer phenotypes; creating a detailed understanding of proteome dynamics would be an enormous scientific advancement in cancer. However, technological challenges, specifically the challenge of analysing single cells and small groups of cells, have delayed progress along these lines. Here, we push the boundaries of proteomic technologies to analyse single cells and small cell populations using mass spectrometry-based proteomics, aiming to better understand cell-cell communication in tumours and follow how these evolve during cancer progression in distinct metastatic locations. We will also develop spatial proteomic approaches to analyse tumours and metastases at a single-cell resolution to identify cellular communities and their functional interactions.
To achieve these goals, we combine technology development toward deep single-cell analyses, combined analysis of multiplexed imaging and spatial proteomics, and computational developments to elucidate cell-cell interactions.
Our research has already established robust and sensitive proteomic approaches that provide deep proteome coverage of single and small cell populations from mouse models and clinical samples. In addition, we developed a new algorithm to elucidate cellular interactions in the tumour microenvironment. These results form the basis for understanding cancer dynamics. We anticipate that these results will have a significant impact on cancer research and will potentially evolve to the development of novel therapeutic approaches in cancer.
