Metastasis by Design: Organ-Specific Adaptation in Cancer Spread

The microenvironments of primary tumors and their metastases often differ substantially, requiring cancer cells to adapt in order to successfully colonize distant organs. Our work investigates the mechanisms underlying metastatic predilection and metabolic adaptation, with a focus on brain metastases (BM) and liver metastases (LM). Analyzing data from over 600,000 cancer samples, we show that BM consistently exhibit high tumor mutational burden (TMB) across cancer types, suggesting increased immunogenicity. Pathway enrichment analysis revealed significant involvement of the mTOR pathway. Notably, we observed differential expression of STK11 (LKB1), a key metabolic regulator, in LM compared to BM. These findings underscore organ-specific adaptations that may inform site-directed therapeutic strategies.