Boussios Stergios, Ozturk Mehmet Akif, Moschetta Michele, Karathanasi Afroditi, Zakynthinakis-Kyriakou Nikolaos, Katsanos Konstantinos H, Christodoulou Dimitrios K, Pavlidis Nicholas
Acute Oncology Assessment Unit, Medway NHS Foundation Trust, Windmill Road, ME7 5NY, Gillingham, Kent, UK.
AELIA Organization, 9th Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece.
J Pers Med. 2019 Feb 7;9(1):12. doi: 10.3390/jpm9010012.
Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase () pathway genes , , and represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments.
结直肠癌（CRC）是全球第三大常见恶性肿瘤。手术仍然是非转移性CRC最重要的治疗方法，辅助化疗的应用主要取决于疾病分期，而疾病分期仍是最强的预后因素。由于下一代测序技术的广泛应用，最近对CRC的基因组学有了更深入的了解，这可能对未来的治疗产生影响。微卫星不稳定性（MSI）已被认为是实体瘤（包括CRC）对抗程序性细胞死亡蛋白1（PD-1）治疗反应的预测标志物。需要注意的是，并非所有具有MSI表型的癌症都对抗PD-1免疫疗法有反应，这凸显了对更好的预测生物标志物的迫切需求。丝裂原活化蛋白激酶（MAPK）通路基因KRAS、NRAS和BRAF是重要的分子靶点，可作为CRC的独立预后生物标志物，并确定那些可能从抗表皮生长因子受体（EGFR）治疗中获益的患者。新出现的证据表明，包括血细胞比例在内的炎症标志物在CRC患者的预后和生存中起着重要作用；这些生物标志物可以在常规血液检查中轻松评估，并用于识别高危患者或更可能从化疗、靶向治疗以及潜在的免疫治疗中获益的患者。对游离DNA（cfDNA）、循环肿瘤细胞（CTC）和/或微小RNA（miRNA）的分析可为CRC的早期诊断、微小残留病的识别以及早期CRC患者复发风险的评估提供有用信息。甚至利用预测性miRNA生物标志物来选择适合新靶向治疗的患者也成为可能。最后，治疗后出现化疗耐药克隆导致治疗耐药的发生仍然是临床实践中最重要的挑战。在这种情况下，识别潜在的生物标志物和治疗靶点至关重要，这可能会带来新的、更有效的治疗方法的开发。
