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Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal
Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
School of Law, University of California, Berkeley, CA 94704, USA
Division of Medical Oncology, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo 04037-004, Brazil
Precision Oncology & Health Economics Group (ONCOPRECH), Post-Graduation Program in Medicine, Nine of July University (UNINOVE), São Paulo 01525-000, Brazil
CNC—Center for Neuroscience and Cell Biology, CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
IIIUC—Institute of Interdisciplinary Research, University of Coimbra, 3004-517 Coimbra, Portugal
Champalimaud Research Program, Champalimaud Center for the Unknown, 1400-038 Lisbon, Portugal
Authors to whom correspondence should be addressed.
Curr. Oncol. 2021, 28(6), 4874-4893;
Received: 1 October 2021 / Revised: 12 November 2021 / Accepted: 17 November 2021 / Published: 20 November 2021
Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well. View Full-Text
Keywords: colorectal cancer; epigenetic testing; screening; diagnosis; CRC biomarkers colorectal cancer; epigenetic testing; screening; diagnosis; CRC biomarkers
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MDPI and ACS Style

Almeida-Lousada, H.; Mestre, A.; Ramalhete, S.; Price, A.J.; de Mello, R.A.; Marreiros, A.D.; Neves, R.P.d.; Castelo-Branco, P. Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers? Curr. Oncol. 2021, 28, 4874-4893.

AMA Style

Almeida-Lousada H, Mestre A, Ramalhete S, Price AJ, de Mello RA, Marreiros AD, Neves RPd, Castelo-Branco P. Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers? Current Oncology. 2021; 28(6):4874-4893.

Chicago/Turabian Style

Almeida-Lousada, Hélder, André Mestre, Sara Ramalhete, Aryeh J. Price, Ramon A. de Mello, Ana D. Marreiros, Ricardo P.d. Neves, and Pedro Castelo-Branco. 2021. "Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?" Current Oncology 28, no. 6: 4874-4893.

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