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Cancer organoids to model therapy response

Previously, we briefly commented on the interest generated by the significant study by Georgios Vlachogiannis and co-workers at the Institute of Cancer Research in London, “Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.” This post looks in a bit more detail at this paper which was published in Science on February 23rd, and which supports the evidence that patient-derived organoids are emerging as a relevant and exciting methodology to help develop preclinical diagnostic models for the development of anti-cancer drugs.

Intestinal organoid

Vlachogiannis and co-workers have described a comprehensive piece of work characterising and evaluating patient-derived organoids (PDO) from gastrointestinal cancer patients participating in Phase 1/2 clinical trials.

This paper has  four key aspects:

  • Firstly, that organoids can be established from patients’ metastasised tumour sites, not solely the primary tumour.
  • Secondly, that the patient-derived organoids have genetic, physical and molecular characteristics that are very similar to the patients’ tumour tissue. This opens the door to the use of these PDOs as mimics and models for patient tumours.
  • Thirdly, this study has shown how these PDOs can be used in 3D drug screening assays. The PDOs responded to a library of 55 drugs (used in clinical trials or clinical practice), with a very strong correlation between the replicate assays. The molecular analysis of the PDOs in the screening assays indicate this approach could be used to determine the susceptibility of patients’ tumours to drug treatment.
  • Finally, this paper reported the responses of the PDO panel to four anticancer drugs and compared it with the patients’ responses in the clinical trials. The organoid responses showed a strong overlap with the drug results in the patients: the comparison between the PDOs’ and patients’ response showed 100% sensitivity, 93% specificity, 88% positive prediction and 100% negative prediction.

The authors conclude that this study suggests that “PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.”