Molecular pathways and targeted therapies in colorectal liver metastasis: from bench to bedside

Colorectal liver metastasis (CRLM) is a major complication of colorectal cancer (CRC), significantly affecting prognosis and survival. Despite advancements in treatment, the management of CRLM remains challenging, primarily due to the complex molecular mechanisms involved. The key molecular pathways that contribute to CRLM development include the Wnt/β-catenin signaling, epidermal growth factor receptor (EGFR), and angiogenesis pathways. These pathways regulate critical processes such as tumor cell proliferation, invasion, and metastasis, and are central to the formation and progression of CRLM. Advances in molecular biology have provided a deeper understanding of these pathways, enabling the development of targeted therapies aimed at improving treatment outcomes. This review presents a detailed analysis of the molecular pathways involved in CRLM, the current status of targeted therapies, and ongoing challenges in the treatment of CRLM. We examine preclinical and clinical developments in targeting these pathways, including Wnt pathway inhibitors, EGFR inhibitors, and anti-angiogenic therapies. In addition, the review discusses ongoing challenges, such as resistance mechanisms, and the potential for combination therapies to improve clinical outcomes. Ultimately, this article highlights the promise of personalized approaches, where molecular profiling can guide therapeutic choices to improve patient outcomes.