Editors' ChoiceCancer

Colorectal cancer in miniature

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Science Translational Medicine  27 May 2015:
Vol. 7, Issue 289, pp. 289ec85
DOI: 10.1126/scitranslmed.aac5085

Precision medicine in oncology aims to tailor cancer treatment to patients. The key challenge in precision medicine is identifying information that can be used as a basis for treatment choice. A major research focus has been to tailor treatment according to tumor mutations and gene expression profiles. However, mutations may cooperate in complex ways, compounded by variable expression, generating unique tumor behavior that cannot be predicted from mutations and expression profiles.

Similar challenges exist in microbiology, in which the solution has been to perform functional assays. In routine clinical practice, drug sensitivity is evaluated in bacterial cultures derived from individual patients. A similar approach might be applicable in oncology, where one could test in vitro drug responses of tumor-derived cell lines from individual patients. Now, a collaboration between three giants in biomedical research—the Hubrecht, Broad, and Sanger Institutes—demonstrates that such an approach might be feasible in colorectal cancer.

Van de Wetering et al. succeeded in prospectively deriving tumor organoids from 20 consecutive patients suffering from colorectal cancer. Organoids are three-dimensional cultures that are thought to recapitulate cell behavior more faithfully than conventional cultures. An important feature of organoids is that they can be perpetuated indefinitely. By contrast, conventional patient-derived tumor cell lines will usually only survive several passages, limiting their use in drug-sensitivity assays. Van de Wetering et al. were able to generate tumor organoid lines from every patient. This in itself is a remarkable achievement because generating ordinary cultures from human tumors is notoriously difficult and inefficient. For many patients, Van de Wetering et al. were also able to derive organoids from noncancerous colorectal tissue, which are the ideal functional controls. In further experiments, the investigators found that the tumor organoids resembled the different types of primary colorectal tumors in terms of mutations and gene expression profiles. Last, they demonstrated the feasibility of performing a 83-compound drug screen on each of these organoid lines, which may form the basis of personalized treatment plans.

Whether the approach of Van de Wetering et al. can be translated into benefits for patients remains to be seen. The importance of their study is that it defines a plausible and feasible approach to tailoring treatment to individual patients.

M. van de Wetering et al., Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161,933–945 (2015). [Abstract]

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