Proteomic Analysis of Cell communication in Tumors

Introduction

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 impact the cancer phenotype and create heterogeneous tumours that evolve in space and time.

Tumour Heterogeneity

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 the development of novel therapeutic approaches.

Proteomic Level Investigation

Although tumour heterogeneity has been thoroughly investigated at the genomic and transcriptomic levels, limited studies have investigated heterogeneity at the proteomic level. Changes in protein expression are central determinants of cancer phenotypes; developing a detailed understanding of proteome dynamics would be an enormous scientific advancement in the cancer field.

Technological Challenges

However, technological challenges, and specifically, the challenge of analysing single cells and small groups of cells, have delayed progress along these lines. Here, I propose to combine my cutting-edge clinical proteomic expertise and extensive experience in cancer biology to study the spatial and temporal heterogeneity of cancer at the proteomic level.

Proposed Methodology

1. We will push the boundaries of the technology towards assaying thousands of proteins from single cells and small groups of cells from in-vivo samples.
2. We will combine microfluidic probe technology to map primary tumors and metastases at high spatial resolution.
3. We will study mouse models of melanoma and breast cancer to follow temporal changes in metastatic growth and treatment response.

Expected Outcomes

This breakthrough in proteomic analysis of cancer dynamics will provide the basis for targeting treatment-resistant metastatic cell populations towards advanced personalized treatment.