Introduction: Colorectal cancer (CRC) exemplifies how precision medicine translates molecular insight into tangible benefits, offering more time, improved quality of life, and personalized care. Foundational discoveries in genomic and epigenetic instability (CIN, MSI, CIMP) and the routine use of extended RAS, BRAF, and MSI/dMMR testing now underpin therapeutic decision-making. In metastatic CRC, molecular stratification guides the use of anti-EGFR and anti-angiogenic therapies, as well as BRAF V600E-directed combinations, which have improved disease control and survival. Immunotherapy has reshaped the landscape for the dMMR/MSI-H subset, enabling deep and durable responses. Minimally invasive liquid biopsies, including circulating tumor DNA (ctDNA), are increasingly used to detect minimal residual disease and monitor clonal evolution. Next-generation platforms like single-cell omics and patient-derived organoids promise more accurate drug response prediction. Biomarker-driven prevention and early detection remain urgent priorities. Altogether, CRC precision medicine is advancing from static genotyping toward a dynamic, lifelong continuum of care that integrates tumor genomics, immune contexture, and real-time monitoring.
Methods: Our approach is based on a comprehensive review of the latest research and clinical guidelines in the field of colorectal cancer precision medicine. We analyzed key foundational discoveries in genomic and epigenetic instability, focusing on CIN, MSI, and CIMP. We examined the routine use of extended RAS, BRAF, and MSI/dMMR testing and their role in therapeutic decision-making for metastatic CRC. Furthermore, we investigated the impact of immunotherapy on the dMMR/MSI-H subset of patients and reviewed ongoing efforts to overcome resistance and extend benefits to pMMR/MSS tumors. The study also explores the role of minimally invasive liquid biopsies and next-generation platforms like single-cell and spatial omics, as well as patient-derived organoids, in predicting drug response and accelerating the bench-to-bedside feedback loop.
Results: Precision medicine has significantly improved outcomes in CRC by guiding targeted therapies. The routine use of extended RAS, BRAF, and MSI/dMMR testing has led to more effective therapeutic choices, including anti-EGFR agents and BRAF V600E-directed combinations, which have increased disease control and survival. Immunotherapy has proven highly effective in dMMR/MSI-H tumors, yielding deep and durable responses. Liquid biopsies, particularly ctDNA analysis, have emerged as a powerful tool for detecting minimal residual disease and monitoring clonal evolution, enabling timely therapy adjustments. Next-generation platforms and patient-derived organoids show promise for more accurate drug response prediction and the discovery of novel therapeutic combinations. These advancements highlight a shift from "one-size-fits-all" treatment toward a targeted, adaptive, and personalized continuum of care.
Conclusion: In conclusion, precision medicine has fundamentally transformed the management of colorectal cancer by integrating molecular insights into clinical practice. The routine use of genomic and epigenetic testing has allowed for the effective stratification of patients, guiding the use of targeted therapies and immunotherapy to improve survival and quality of life. The emergence of liquid biopsies and next-generation platforms holds great promise for dynamic, real-time monitoring and adaptive therapeutic strategies. Despite these significant advancements, the challenge of equitable access to these sophisticated diagnostics and therapies remains a critical priority. Ultimately, the field is evolving toward a deeply personalized and adaptive model of care that integrates an individual’s unique biology with their values and preferences, setting a new standard for cancer treatment.