The following article features coverage from the American Association for Cancer Research (AACR) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Liquid biopsy at disease progression revealed at least 1 validated mechanism of acquired resistance to targeted therapy in three-quarters of patients with molecularly defined subtypes of gastrointestinal cancers, according to results of a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2019.

Although it has been proposed that DNA sequencing of circulating cell-free tumor DNA (cfDNA) at the time of disease progression may offer advantages (beyond ease of sampling) over assays that use solid tumor specimens — prospective evidence involving a comparison of these 2 approaches is lacking in this setting.

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In this study, circulating tumor cfDNA sequencing was performed at disease progression to targeted therapy on plasma specimens from 44 patients with 7 different molecularly defined subgroups of gastrointestinal cancers. At least 1 resistance mechanism and more than 1 mechanism of acquired resistance was identified in 75% and 52% of patients, respectively.

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In contrast, for the 23 patients in whom DNA sequencing was also performed on matched postprogression tumor biopsy specimens, at least 1 and more than 1 mechanism of acquired resistance was identified in 48% and 9% of patients, respectively.

In addition, for 78% of patients with matched plasma and tumor specimens, circulating cfDNA sequencing identified at least 1 mechanism of acquired resistance not identified by tumor DNA sequencing.

The researchers also reported that results of serial DNA sequencing of multiple specimens of circulating cfDNA and solid tumor, collected over time in the postprogression setting, as well as DNA sequencing performed on specimens collected shortly after death in selected cases, revealed evidence for tumor heterogeneity that was captured by circulating cfDNA sequencing.

“These data illustrate that acquired resistance is characterized by frequent and profound tumor heterogeneity, and suggests that liquid biopsy may more effectively identify heterogeneous clinically relevant resistance alterations compared to standard tumor biopsy,” the researchers noted in conclusion.

Read more of Cancer Therapy Advisor‘s coverage of AACR 2019 meeting by visiting the conference page.


  1. Parikh AR, Leshchiner I, Elagina L, et al. Liquid biopsy versus tissue biopsy to assess acquired resistance and tumor heterogeneity in gastrointestinal cancers. Presented at: American Association for Cancer Research (AACR) 2019; March 29-April 3, 2019; Abstract LB257/3.