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Review
. 2015;15(12):1631-44.
doi: 10.1586/14737159.2015.1110021. Epub 2015 Nov 11.

Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet?

Jiri Polivka Jr  1   2 , Martin Pesta  3 , Filip Janku
Affiliations
Review

Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet?

Jiri Polivka Jr et al. Expert Rev Mol Diagn. 2015.

Abstract

The optimal choice of cancer therapy depends upon analysis of the tumor genome for druggable molecular alterations. The spatial and temporal intratumor heterogeneity of cancers creates substantial challenges, as molecular profile depends on time and site of tumor tissue collection. To capture the entire molecular profile, multiple biopsies from primary and metastatic sites at different time points would be required, which is not feasible for ethical or economic reasons. Molecular analysis of circulating cell-free DNA offers a novel, minimally invasive method that can be performed at multiple time-points and plausibly better represents the prevailing molecular profile of the cancer. Molecular analysis of this cell-free DNA offers multiple clinically useful applications, such as identification of molecular targets for cancer therapy, monitoring of tumor molecular profile in real time, detection of emerging molecular aberrations associated with resistance to particular therapy, determination of cancer prognosis and diagnosis of cancer recurrence or progression.

Keywords: Liquid biopsy; advanced cancer; cell-free DNA; personalized medicine; targeted therapy.

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Conflict of interest statement

Financial & competing interests disclosure The authors were supported by MH CZ - DRO (Faculty Hospital Plzen - FNPl, 00669806) and by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic, the Elsa U. Pardee Foundation, the Sidney Kimmel Foundation for Cancer Research, the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy, the U.S. National Center for Advancing Translational Sciences (grant no. UL1 TR000371), and the U.S. National Institutes of Health through MD Anderson’s Cancer Center Support Grant (P30 CA016672). F Janku received research support from Biocartis (Mechelen, Belgium), Trovagene (San Diego, CA, USA) and Illumina (San Diego) and is on the Scientific Advisory Board of Trovagene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1
Figure 1
Passive (from apoptotic and necrotic cells) and active release of DNA fragments from tumor cells into the circulation. This cell-free DNA can be used for testing of tumor-specific aberrations.
See this image and copyright information in PMC

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