Multiomic Approaches to Illuminate Molecular Drivers of Breast Cancer Metastasis to the Liver 

The mechanisms driving metastatic progression in breast cancer (BC) remain poorly understood, hindering the development of effective therapies. Liver metastases, which account for 30% of metastatic BC cases, present a significant therapeutic challenge, with surgical resection often ineffective. There is currently no standard of care for BC liver metastasis, and treatment is guided by molecular profiling of primary and metastatic tumors. The lack of reliable human experimental models for studying metastasis underscores the need for better models to explore the molecular interactions underlying BC metastasis.

• This study uses multiomic analysis of breast cancer patient-derived xenograft (PDX) models from primary tumors and liver metastases to uncover molecular mechanisms of liver colonization by BC cells.

• The results reveal significant molecular differences between primary BC tumors and liver metastases, with key genes identified at the DNA, RNA, and protein levels that support BC cell adaptation in the liver.

• These findings provide new insights into the mechanisms of BC liver metastasis and highlight potential therapeutic targets for future treatment interventions.