Topic: From Clinic Molecular Pathology to Precision Medicine – Exploring Tumor Microenvironment of Liver Metastasis

Liver metastasis occurs when cancer spreads from its primary site to the liver. As one of the most common sites for metastatic disease, the liver's unique blood supply and function as a filtration organ make it particularly susceptible to metastasis. Understanding the mechanisms and biology of liver metastasis is critical for improving treatment strategies and patient outcomes. Primary cancers commonly associated with liver metastases include colorectal cancer, breast cancer, pancreatic cancer, melanoma, and lung cancer. Notably, more than 50% of colorectal cancer patients develop liver metastases, making it a leading cause of cancer-related mortality. The process of liver metastasis involves distinct steps in the metastatic cascade: Detachment from the Primary Tumor: Tumor cells invade surrounding tissues and enter the bloodstream  (intravasation). Survival in Circulation: Cancer cells evade immune surveillance and withstand mechanical stresses. Extravasation into the Liver: Tumor cells adhere to the liver sinusoidal endothelium and migrate into the liver parenchyma. Colonization: Cancer cells establish and proliferate within the liver's unique microenvironment.

The tumor microenvironment (TME) of liver metastases plays a pivotal role in cancer progression and therapeutic responses. It involves a complex interplay between cancer cells, stromal cells, immune cells, and the extracellular matrix (ECM) within the liver's distinctive physiological context. Understanding the cellular and molecular components of the TME is essential for developing innovative therapeutic strategies. Emerging technologies like spatial transcriptomics and integrative modeling hold significant promise for personalizing treatment approaches targeting the TME. Additionally, the liver microenvironment itself plays a critical role in determining the success of liver metastasis by shaping tumor cell behavior and immune responses.

Management of liver metastasis is multifaceted and depends on factors such as the type of primary cancer, the size and number of metastatic lesions, the patient's overall health, and the presence of metastases in other organs. Systemic therapy forms the cornerstone of treatment, especially for patients with widespread disease. An integrative approach combining systemic therapies, surgical interventions, and liver-directed techniques is essential for effective management. Advances in precision medicine and targeted therapies have significantly improved survival and quality of life for patients with metastatic liver disease. Early diagnosis and continuous monitoring remain critical for optimizing outcomes. This Special Issue will delve into the latest advancements in liver metastasis research, focusing on clinical and pathological patterns, systemic therapies like immune checkpoint inhibitors and CAR-T cell therapies, and combination strategies targeting both the immune system and the TME. These insights are vital for identifying novel biomarkers and therapeutic targets to develop personalized treatments that enhance survival outcomes for patients with liver metastases.

We invite contributions from researchers across diverse fields addressing various aspects of liver metastasis, from clinical molecular pathology to precision medicine, and from basic science to clinical trials. This Special Issue aims to foster interdisciplinary collaboration, accelerating the development of more effective and personalized therapeutic strategies for liver metastasis. It will provide a comprehensive overview of the current landscape and future directions in the field. The Special Issue seeks to bring together cutting-edge research, clinical  trials, and emerging therapies, encouraging collaboration among experts in cancer biology, molecular pathology, immunology, oncology, and hepatology. Contributions addressing challenges and opportunities in liver metastasis are encouraged, with the shared goal of advancing the fight against this formidable disease.

Potential topics include, but are not limited to:

1. Clinical molecular pathology of liver metastases from various tumors;
2. Clinical management and precision medicine approaches for liver metastasis;
3. Biomarkers for precision diagnosis and prognosis of liver metastasis;
4. Tumor microenvironment and immunotherapy in liver metastasis;
5. Metabolic reprogramming and proteomics of liver metastasis;
6. Interventional imaging and therapy for liver metastasis;
7. Neoantigens and cancer vaccines in liver metastases from different cancers;
8. Exploration of combination treatment strategies for liver metastasis;
9. Applications of gene and cell therapy in liver metastases from various cancers;
10. Neoadjuvant and conversion therapies for liver metastasis.