Circulating Tumor DNA: An Emerging Tool in Gastrointestinal Cancers

Author:

Alese Olatunji B.1,Cook Natalie23,Ortega-Franco Ana2,Ulanja Mark B.4,Tan Lavinia56,Tie Jeanne567

Affiliation:

1. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA

2. Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, United Kingdom

3. Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom

4. Christus Ochsner St. Patrick Hospital, Lake Charles, LA

5. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

6. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

7. Division of Personalized Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Abstract

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that has come from primary or metastatic cancer sites. Neoplasm-specific genetic and epigenetic abnormalities are increasingly being identified through liquid biopsy: a novel, minimally invasive technique used to isolate and analyze ctDNA in the peripheral circulation. Liquid biopsy and other emerging ctDNA technologies represent a paradigm shift in cancer diagnostics because they allow for the detection of minimal residual disease in patients with early-stage disease, improve risk stratification, capture tumor heterogeneity and genomic evolution, and enhance ctDNA-guided adjuvant and palliative cancer therapy. Moreover, ctDNA can be used to monitor the tumor response to neoadjuvant and postoperative therapy in patients with metastatic disease. Using clearance of ctDNA as an endpoint for escalation/de-escalation of adjuvant chemotherapy for patients considered to have high-risk disease has become an important area of research. The possibility of using ctDNA as a surrogate for treatment response–including for overall survival, progression-free survival, and disease-free survival–is an attractive concept; this surrogate will arguably reduce study duration and expedite the development of new therapies. In this review, we summarize the current evidence on the applications of ctDNA for the diagnosis and management of gastrointestinal tumors. Gastrointestinal cancers–including tumors of the esophagus, stomach, colon, liver, and pancreas–account for one-quarter of global cancer diagnoses and contribute to more than one-third of cancer-related deaths. Given the prevalence of gastrointestinal malignancies, ctDNA technology represents a powerful tool to reduce the global burden of disease.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

General Medicine

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