Agnostic Biomarkers and Molecular Signatures in Colorectal Cancer-Guiding Chemotherapy and Predicting Response

The concept of agnostic biomarkers-molecular modifications that guide therapy irrespective of tumor origin-has gained increasing relevance in oncology, including colorectal cancer (CRC). This review aims to critically evaluate the role of such biomarkers in CRC, highlighting their clinical significance as therapeutic targets and indicators of prognosis. Through a PubMed search using the terms "agnostic treatment AND colorectal cancer," eight key studies were identified and qualitatively analyzed. We focus on several biomarkers commonly regarded as agnostic across tumor types, including BRAF V600E mutation, receptor tyrosine kinase (RTK) and PI3K fusions, the CpG island methylator phenotype (CIMP), high tumor mutational burden (TMB), and microsatellite instability (MSI). These markers are inspected for their prevalence in CRC, underlying pathophysiological mechanisms of cancer promotion, and predictive or prognostic implications. Moreover, we integrate findings from broader oncologic studies to contextualize the evolving role of agnostic biomarkers beyond organ-specific paradigms. Emerging evidence suggests that leveraging these molecular signatures may inform the use of targeted and immunotherapeutic agents as first-line options in select CRC populations. Collectively, agnostic biomarkers represent an auspicious avenue for personalizing CRC treatment, particularly in advanced-stage disease where traditional treatment options remain limited.