Biomarkers in Metastatic Colorectal Cancer: Status Quo and Future Perspective

Abstract

Colorectal cancer (CRC) is the third most frequent cancer worldwide, and its incidence is steadily increasing. During the last two decades, a tremendous improvement in outcome has been achieved, mainly due to the introduction of novel drugs, targeted treatment, immune checkpoint inhibitors (CPIs) and biomarker-driven patient selection. Moreover, progress in molecular diagnostics but also improvement in surgical techniques and local ablative treatments significantly contributed to this success. However, novel therapeutic approaches are needed to further improve outcome in patients diagnosed with metastatic CRC. Besides the established biomarkers for mCRC, such as microsatellite instability (MSI) or mismatch repair deficiency (dMMR), RAS/BRAF, sidedness and HER2 amplification, new biomarkers have to be identified to better select patients who derive the most benefit from a specific treatment. In this review, we provide an overview about therapeutic relevant and established biomarkers but also shed light on potential promising markers that may help us to better tailor therapy to the individual mCRC patient in the near future.

Survival Contradiction in Stage II, IIIA, And IIIB Colon Cancer: A Surveillance, Epidemiology, and End Result-Based Analysis

“…Higher T staging not only means a larger primary tumor but also refects stronger aggressiveness [29]. At the same time, the ratio of microsatellite instability [30][31][32] and perineural invasion in T4N0 colon cancer was signifcantly increased [33], suggesting that stage IIB and stage IIC tumors may have diferent biological behaviors compared with stage III.…”

Colorectal Cancer Liver Metastases: Genomics and Biomarkers with Focus on Local Therapies

“…Elevated carcinoembryonic antigen (CEA) levels have been associated with poor prognosis and shorter OS following CRC resection. Of note, CEA levels can be elevated in other malignancies and inflammatory states, and therefore CEA is not a specific diagnostic biomarker [ 26 ]. Lack of normalization of CEA levels following resection is likely the result of inadequate resection and presence of metastatic disease.…”

“…Finally, MSI-H/dMMR status increased the ability to predict response to checkpoint inhibitors [ 77 , 78 ]. Patients previously treated for MSI-H/dMMR mCRC experienced a 30% plateau in OS and progression-free survival (PFS) at five years in the phase II KEYNOTE-164 study [ 26 , 79 ].…”

Development of a Novel Anti-CD44 Variant 6 Monoclonal Antibody C44Mab-9 for Multiple Applications against Colorectal Carcinomas

“…Therefore, the large-scale data analysis by an international consortium classified the CRC into four consensus molecular subtypes, including the microsatellite instability immune, the canonical, the metabolic, and the mesenchymal types [ 3 ]. In addition, various marker proteins have been investigated for the prediction of prognosis and drug responses of CRC [ 4 , 5 ]. Among them, recent studies suggest that CD44 plays a critical role in tumor progression through its cancer-initiating and metastasis-promoting properties [ 6 ].…”