Oncotarget

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Circulating tumor DNA analysis in the era of precision oncology

Rabih Said, Nicolas Guibert, Geoffrey R. Oxnard and Apostolia M. Tsimberidou _

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Oncotarget. 2020; 11:188-211. https://doi.org/10.18632/oncotarget.27418

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Abstract

Rabih Said1,2,*, Nicolas Guibert3,4,*, Geoffrey R. Oxnard3 and Apostolia M. Tsimberidou1

1 Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2 Department of Oncology, St. George Hospital University Medical Center, University of Balamand, Beirut, Lebanon

3 Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

4 Thoracic Oncology, Toulouse University Hospital, Toulouse, France

* Co-authorship

Correspondence to:

Apostolia M. Tsimberidou,email: atsimber@mdanderson.org

Keywords: circulating tumor DNA analysis; clinical trials; targeted therapy; genomic profiling

Received: August 01, 2019     Accepted: December 16, 2019     Published: January 14, 2020

ABSTRACT

The spatial and temporal genomic heterogeneity of various tumor types and advances in technology have stimulated the development of circulating tumor DNA (ctDNA) genotyping. ctDNA was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is associated with significant risk, when tumor tissue is insufficient or inaccessible, and/or when repeated assessment of tumor molecular abnormalities is needed to optimize treatment. The role of ctDNA is now well established in the clinical decision in certain alterations and tumors, such as the epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer and the v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in colorectal cancer. The role of ctDNA analysis in other tumor types remains to be validated. Evolving data indicate the association of ctDNA level with tumor burden, and the usefulness of ctDNA analysis in assessing minimal residual disease, in understanding mechanisms of resistance to treatment, and in dynamically guiding therapy. ctDNA analysis is increasingly used to select therapy. Carefully designed clinical trials that use ctDNA analysis will increase the rate of patients who receive targeted therapy, will elucidate our understanding of evolution of tumor biology and will accelerate drug development and implementation of precision medicine. In this article we provide a critical overview of clinical trials and evolving data of ctDNA analysis in specific tumors and across tumor types.


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