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3-D 'organoids' grown from patient tumors could personalize
drug screening
Three-dimensional cultures (or "organoids") derived from the tumors
of cancer patients closely replicate key properties of the original
tumors, reveals a study published May 7 in Cell. These "organoid"
cultures are amenable to large-scale drug screens for the detection
of genetic changes associated with drug sensitivity and pave the
way for personalized treatment approaches that could optimize
clinical outcomes in cancer patients.
"This is the first time that a collection of cancer organoids, or a living
biobank, has been derived from patient tumors," says senior study
author Mathew Garnett, a geneticist at the Wellcome Trust Sanger
Institute. "We believe that these organoids are an important new
tool in the arsenal of cancer biologists and may ultimately improve our ability to develop more
effective cancer treatments."
To study the causes of cancer and develop new cancer treatments, many laboratories use
experimental model systems such as cells grown from patient tumors. However, currently available
cell lines have been derived under suboptimal conditions and therefore fail to reflect important
features of tumor cells. As a result, it has been challenging to predict the drug sensitivity of individual
patients based on their unique spectrum of genetic mutations.
In recent years, scientists have developed organoid cell culture systems as an alternative approach to
grow normal and diseased tissue in a dish. In contrast to cell lines, organoids display the hallmarks of
the original tissue in terms of its 3D architecture, the cell types present, and their self-renewal
properties. Given the advantages of organoids, Garnett and Hans Clevers of the Hubrecht Institute
set out to test whether these cultures could potentially bridge the gap between cancer genetics and
patient outcomes.
In the new study, the researchers grew 22 organoids derived from tumor tissue from 20 patients with
colorectal cancer and then sequenced genomic DNA isolated from these cultures. The genetic
mutations in the organoid cultures closely matched those in the corresponding tumor biopsies and
agreed well with previous large-scale analyses of colorectal cancer mutations. These findings confirm
that the cultures faithfully capture the genomic features of the tumors from which they are derived as
well as much of the genomic diversity associated with colorectal cancer.
To link drug sensitivity to genetic changes, the researchers next screened the responses of the
organoids to 83 experimental and approved cancer drugs. Given their diverse genetic profiles, the
organoids displayed a range of sensitivities to the drugs. In validation of the approach, the
researchers identified previously reported associations between specific mutations and resistance to
particular drugs. The organoids also revealed a novel gene-drug association, indicating that the
subset of cancer patients with RNF43 mutations would strongly benefit from a drug that inhibits a
protein called porcupine. "At some point in the future, this approach may be suitable for modeling
individual patient response to cancer therapies to inform clinical treatment," Garnett says.
Moving forward, the researchers plan to expand the panel of existing colon organoids as well as
develop an organoid biobank for other tumor types. "Cancer is a diverse and complex disease and
having a large collection of organoids is necessary to encompass this diversity to enable scientists
and clinicians to develop new treatments," Garnett says.
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Cell, van de Wetering et al.: "Prospective derivation of a Living Organoid Biobank of colorectal cancer
patients" http://dx.doi.org/10.1016/j.cell.2015.03.053
Co-author Matthew Meyerson receives a commercial research grant from Bayer and has ownership
interest (including patents) in and is a consultant/advisory board member for Foundation Medicine.
To view video footage and interviews with the researchers courtesy of the Wellcome Trust Sanger
Institute, please visit: https://www.youtube.com/watch?v=DH9m-4bRYOc&feature=youtu.be
To access a PDF the paper proof, please visit this
Dropbox: https://www.dropbox.com/sh/buz2738y50npjgl/AAChj-dZPkwSH_TG-UJdHNkna?dl=0 Or
contact Joseph Caputo at jcaputo@cell.com.
Author Contacts:
Mathew Garnett
Wellcome Trust Sanger Institute
mg12@sanger.ac.uk
+44 (0)1223 494878
NOTE: Traveling on May 7 and will have reduced availability.
Hayley Francies
Wellcome Trust Sanger Institute
hf4@sanger.ac.uk
Hans Clevers
Hubrecht Institute
h.clevers@hubrecht.eu
+31 (0)30 212 18 31
Media Contact:
Mary Clarke
Wellcome Trust Sanger Institute
mc19@sanger.ac.uk
+44 (0)1223 492368
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