The Developing Story of Predictive 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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-02-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/9/1/12 |
| _version_ | 1797760815215935488 |
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| author | Stergios Boussios Mehmet Akif Ozturk Michele Moschetta Afroditi Karathanasi Nikolaos Zakynthinakis-Kyriakou Konstantinos H. Katsanos Dimitrios K. Christodoulou Nicholas Pavlidis |
| author_facet | Stergios Boussios Mehmet Akif Ozturk Michele Moschetta Afroditi Karathanasi Nikolaos Zakynthinakis-Kyriakou Konstantinos H. Katsanos Dimitrios K. Christodoulou Nicholas Pavlidis |
| author_sort | Stergios Boussios |
| collection | DOAJ |
| description | 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 (<i>MAPK</i>) pathway genes <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> 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. |
| first_indexed | 2024-03-12T19:05:00Z |
| format | Article |
| id | doaj.art-28fdefdf7cc043c993c924e223bb35a1 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-12T19:05:00Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-28fdefdf7cc043c993c924e223bb35a12023-08-02T06:19:18ZengMDPI AGJournal of Personalized Medicine2075-44262019-02-01911210.3390/jpm9010012jpm9010012The Developing Story of Predictive Biomarkers in Colorectal CancerStergios Boussios0Mehmet Akif Ozturk1Michele Moschetta2Afroditi Karathanasi3Nikolaos Zakynthinakis-Kyriakou4Konstantinos H. Katsanos5Dimitrios K. Christodoulou6Nicholas Pavlidis7Acute Oncology Assessment Unit, Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, Kent, UKDepartment of Internal Medicine, Bahcesehir University School of Medicine, 34353 Istanbul, TurkeyDrug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London W1G 6AD, UKAcute Oncology Assessment Unit, Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, Kent, UKLeicester Diabetes Research Centre, Gwendolen Road, Leicester LE5 4PW, UKDepartment of Gastroenterology, University Hospital of Ioannina, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, GreeceDepartment of Gastroenterology, University Hospital of Ioannina, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, GreeceMedical School, University of Ioannina, Stavros Niarchou Avenue, 45110 Ioannina, GreeceColorectal 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 (<i>MAPK</i>) pathway genes <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> 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.https://www.mdpi.com/2075-4426/9/1/12colorectal cancerbiomarkersprognostic and predictive markerstreatment resistance |
| spellingShingle | Stergios Boussios Mehmet Akif Ozturk Michele Moschetta Afroditi Karathanasi Nikolaos Zakynthinakis-Kyriakou Konstantinos H. Katsanos Dimitrios K. Christodoulou Nicholas Pavlidis The Developing Story of Predictive Biomarkers in Colorectal Cancer Journal of Personalized Medicine colorectal cancer biomarkers prognostic and predictive markers treatment resistance |
| title | The Developing Story of Predictive Biomarkers in Colorectal Cancer |
| title_full | The Developing Story of Predictive Biomarkers in Colorectal Cancer |
| title_fullStr | The Developing Story of Predictive Biomarkers in Colorectal Cancer |
| title_full_unstemmed | The Developing Story of Predictive Biomarkers in Colorectal Cancer |
| title_short | The Developing Story of Predictive Biomarkers in Colorectal Cancer |
| title_sort | developing story of predictive biomarkers in colorectal cancer |
| topic | colorectal cancer biomarkers prognostic and predictive markers treatment resistance |
| url | https://www.mdpi.com/2075-4426/9/1/12 |
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