Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 May;21(5):440-8.
doi: 10.1038/nm.3841. Epub 2015 Apr 13.

Studying clonal dynamics in response to cancer therapy using high-complexity barcoding

Hyo-eun C Bhang  1 , David A Ruddy  2 , Viveksagar Krishnamurthy Radhakrishna  1 , Justina X Caushi  1 , Rui Zhao  3 , Matthew M Hims  1 , Angad P Singh  1 , Iris Kao  2 , Daniel Rakiec  2 , Pamela Shaw  2 , Marissa Balak  2 , Alina Raza  1 , Elizabeth Ackley  2 , Nicholas Keen  1 , Michael R Schlabach  1 , Michael Palmer  2 , Rebecca J Leary  1 , Derek Y Chiang  1 , William R Sellers  1 , Franziska Michor  3 , Vesselina G Cooke  1 , Joshua M Korn  1 , Frank Stegmeier  1
Affiliations

Studying clonal dynamics in response to cancer therapy using high-complexity barcoding

Hyo-eun C Bhang et al. Nat Med. 2015 May.

Abstract

Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of next-generation sequencing. To address this, we developed a high-complexity barcode library, ClonTracer, which enables the high-resolution tracking of more than 1 million cancer cells under drug treatment. In two clinically relevant models, ClonTracer studies showed that the majority of resistant clones were part of small, pre-existing subpopulations that selectively escaped under therapeutic challenge. Moreover, the ClonTracer approach enabled quantitative assessment of the ability of combination treatments to suppress resistant clones. These findings suggest that resistant clones are present before treatment, which would make up-front therapeutic combinations that target non-overlapping resistance a preferred approach. Thus, ClonTracer barcoding may be a valuable tool for optimizing therapeutic regimens with the goal of curative combination therapies for cancer.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Haematologica. 2013 May;98(5):714-7 - PubMed
    1. Cancer Cell. 2010 Jan 19;17(1):77-88 - PubMed
    1. Sci Transl Med. 2013 Jan 9;5(167):167ra4 - PubMed
    1. Cancer Discov. 2013 Sep;3(9):1030-43 - PubMed
    1. Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1347-52 - PubMed

Publication types

MeSH terms