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

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.

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.