Integrative Profiling of Tumor and Blood Microenvironments to Uncover Molecular and Immune Determinants of Prognosis and Treatment Efficacy in Metastatic Colorectal Cancer

Abstract

Simple Summary Metastatic colorectal cancer is associated with poor prognosis, as patients respond very differently to available therapies, and the disease can change over time. Better biomarkers are needed to help clinicians choose the most effective treatment for each patient and to monitor whether therapy is working. This review summarizes the most promising biomarkers currently being investigated in metastatic colorectal cancer, including those measured in tumor tissue and those detected through blood-based tests. We describe prognostic and predictive markers related to tumor genetics, immune activity, tumor-associated cells, and interactions with the microbiome, as well as emerging metabolic and lipid-related signatures. We also highlight circulating biomarkers such as circulating tumor DNA, immune cell profiling, and circulating tumor cells. Finally, we discuss key limitations preventing clinical implementation and explore how combining multiple biomarker types with artificial intelligence may accelerate the development of reliable tools for personalized cancer treatment.