Dataset Information

Significance of Liquid Biopsy for Monitoring and Therapy Decision of Colorectal Cancer.

ABSTRACT:

Purpose

Despite therapeutic improvements, all patients with nonresectable metastatic colorectal cancer (mCRC) acquire resistance to treatment probably due to the growth of mutated clones. In contrast to tissue-based studies, liquid biopsies have enabled the opportunity to reveal emerging resistance to treatment by detecting mutated clones and noninvasively monitoring clonal dynamics during therapy.

Methods

The courses of three patients with mCRC who were initially RAS wild-type were monitored longitudinally using liquid biopsy with long-term follow-up of up to 20 sequential samples. Detection of fragmented RAS mutated circulating cell-free DNA (cf)DNA in plasma was performed by BEAMing. In addition, plasma digital droplet PCR was used to detect and quantify BRAF and PIK3CA mutated cfDNA. Changes of mutational load were correlated with imaging data.

Results

A combination of liquid biopsy and radiological imaging enabled visualization of the occurrence of clonal redistribution after discontinuation of anti-EGFR mAb therapy, as well as emerging RAS mutations during therapy with anti-EGFR mAb indicating resistance. Furthermore, we found that growth of RAS mutated clones is independent of direct selective pressure by anti-EGFR therapy, which is a significant and new finding of this study.

Conclusions

Our findings demonstrated the whole spectrum of clonal selection and redistribution of mutated cell clones leading to acquired resistance. Given our observation that the growth of RAS mutated clones can evolve even in the absence of anti-EGFR mAb therapy, there is a clear imperative to monitor RAS mutations in serial blood draws in all RAS wild-type patients in general and independent of the therapy.

SUBMITTER: Klein-Scory S

PROVIDER: S-EPMC5789760 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Project description:Simple Summary There are some challenges to improve the clinical outcome of colorectal cancers (CRCs) by implementing new technologies, such as early detection of recurrence/relapse and selection of appropriate drugs based on the genomic profiles of tumors. For example, the genomic characteristics of tumors can be analyzed by blood-based tests, namely ‘liquid biopsies’, which are minimally-invasive and can be performed repeatedly during the treatment course. Hence, liquid biopsies are considered to hold great promise to fill these gaps in clinical routines. In this review, we addressed clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of minimal residual disease, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. Furthermore, we discussed the possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information. Abstract In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades. However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive. We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients. With the recent technological advances in methodologies and bioinformatics, the genomic profiles can be analyzed profoundly without delay by blood-based tests—‘liquid biopsies’. From a clinical point of view, a minimally-invasive liquid biopsy is thought to be a promising method and can be implemented in routine clinical settings in order to meet unmet clinical needs. In this review, we highlighted clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of MRD, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. In addition, we addressed a possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information.