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3D 'organoids' grown from patient tumors

could personalize drug screening
Date:
Source:
Summary:

May 7, 2015
Cell Press
Three-dimensional cultures (or 'organoids') derived from the
tumors of cancer patients closely replicate key properties of
the original tumors, reveals a study. 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.

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that could optimize clinical outcomes in cancer patients.

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3-D organoid cultures derived from healthy and tumor tissue from
colorectal cancer patients are used for a high throughput drug screen
to identify genedrug associations that may facilitate personalized
therapy.
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therapy.
Credit: van de Wetering et al./Cell 2015

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
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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.
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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
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Story Source:
The above story is based on materials provided by Cell Press. Note:
Materials may be edited for content and length.

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Journal Reference:
1. van de Wetering et al. Prospective derivation of a Living
Organoid Biobank of colorectal cancer patients. Cell, May 2015
DOI: 10.1016/j.cell.2015.03.053

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