Kyrochristou Ilektra, Lianos Georgios D, Kyrochristou Gerasimia D, Anagnostopoulos Georgios, Bali Christina, Boussios Stergios, Mitsis Michail, Schizas Dimitrios, Vlachos Konstantinos
Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece.
Department of Surgery, General Hospital of Nikaia and Piraeus, 18454 Athens, Greece.
Biomedicines. 2025 Aug 21;13(8):2038. doi: 10.3390/biomedicines13082038.
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 mutation, receptor tyrosine kinase (RTK) and 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.
无论肿瘤起源如何均可指导治疗的不可知生物标志物（分子修饰）这一概念，在包括结直肠癌（CRC）在内的肿瘤学领域正变得越来越重要。本综述旨在批判性地评估此类生物标志物在结直肠癌中的作用，强调其作为治疗靶点和预后指标的临床意义。通过在PubMed上使用“不可知治疗与结直肠癌”这一检索词进行搜索，确定了八项关键研究并进行了定性分析。我们聚焦于几种通常被视为跨肿瘤类型不可知的生物标志物，包括基因突变、受体酪氨酸激酶（RTK）和融合、CpG岛甲基化表型（CIMP）、高肿瘤突变负担（TMB）以及微卫星不稳定性（MSI）。对这些标志物在结直肠癌中的发生率、癌症发生的潜在病理生理机制以及预测或预后意义进行了考察。此外，我们整合了更广泛肿瘤学研究的结果，以将不可知生物标志物在超越器官特异性模式方面不断演变的作用置于背景之中。新出现的证据表明，利用这些分子特征可能有助于在特定的结直肠癌人群中将靶向治疗和免疫治疗药物作为一线选择。总体而言，不可知生物标志物是实现结直肠癌治疗个体化的一个有前景的途径，尤其是在传统治疗选择仍然有限的晚期疾病中。
