Spatial multiomics to decode and target the non-random metastatic behavior of three common malignancies

Until recently, research on clinical metastases has been hindered by often too sparse metastatic tumor material and previous technical limitations. This has made credible analysis challenging and often impossible.

Recent technological advances, including spatial omics, allow unprecedented in-depth investigation of tumor material, even in limited quantities.

I propose to combine high-resolution spatial whole transcriptomics and multiplex protein imaging on a clinical metastasis cancer cohort of three hundred patients.

The cohort will include bone, brain, liver, and lung metastases from three common malignancies, i.e., melanoma, lung, and breast cancer. In addition, clinicopathological and outcome data will be compiled for all three hundred patients. To guide the bioinformatics analysis, I will specifically look for metastasis site-specific therapeutic targets.

This approach is highly motivated considering the reoccurring spread patterns of different cancer types.

This clinical observation strongly suggests that metastasis colonization is dictated by metastasis site-specific intrinsic or acquired capabilities by tumor cells and non-malignant accessory cells, e.g., immune cells.

I hypothesize that these metastasis site-specific capabilities hide cellular vulnerabilities that could be targeted therapeutically.

Ultimately, the proposal will resolve whether the distant metastatic site needs to be considered for treatment and drug development.