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    3D 'organoids' grown from patient tumorscould personalize drug screening

    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 o timize clinical outcomes in cancer atients.

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    FULL STORY

    3-D organoid cultures derived from healthy and tumor tissue from

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    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 couldoptimize 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 moreeffective 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 Cleversof 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 cancermutations. 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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    Cite This Page:

    Cell Press. "3D 'organoids' grown from patient tumors could personalize

    drug screening." ScienceDaily. ScienceDaily, 7 May 2015.

    .

    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.

    Story Source:

    The above story is based on materialsprovided by Cell Press. Note:

    Materials may be edited for content and length.

    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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