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The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer
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The Developing Story of Predictive Biomarkers in Colorectal Cancer

Acute Oncology Assessment Unit, Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, Kent, UK
AELIA Organization, 9th Km Thessaloniki—Thermi, 57001 Thessaloniki, Greece
Department of Internal Medicine, Bahcesehir University School of Medicine, 34353 Istanbul, Turkey
Drug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London W1G 6AD, UK
Leicester Diabetes Research Centre, Gwendolen Road, Leicester LE5 4PW, UK
Department of Gastroenterology, University Hospital of Ioannina, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Medical School, University of Ioannina, Stavros Niarchou Avenue, 45110 Ioannina, Greece
Author to whom correspondence should be addressed.
J. Pers. Med. 2019, 9(1), 12;
Received: 24 November 2018 / Revised: 28 January 2019 / Accepted: 4 February 2019 / Published: 7 February 2019
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
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 (MAPK) pathway genes KRAS, NRAS, and BRAF 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. View Full-Text
Keywords: colorectal cancer; biomarkers; prognostic and predictive markers; treatment resistance colorectal cancer; biomarkers; prognostic and predictive markers; treatment resistance
MDPI and ACS Style

Boussios, S.; Ozturk, M.A.; Moschetta, M.; Karathanasi, A.; Zakynthinakis-Kyriakou, N.; Katsanos, K.H.; Christodoulou, D.K.; Pavlidis, N. The Developing Story of Predictive Biomarkers in Colorectal Cancer. J. Pers. Med. 2019, 9, 12.

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