Systematic review: predictive value of organoids in colorectal cancer

Abstract

While chemotherapy alone or in combination with radiotherapy and surgery are important modalities in the treatment of colorectal cancer, their widespread use is not paired with an abundance of diagnostic tools to match individual patients with the most effective standard-of-care chemo- or radiotherapy regimens. Patient-derived organoids are tumour-derived structures that have been shown to retain certain aspects of the tissue of origin. We present here a systematic review of studies that have tested the performance of patient derived organoids to predict the effect of anti-cancer therapies in colorectal cancer, for chemotherapies, targeted drugs, and radiation therapy, and we found overall a positive predictive value of 68% and a negative predictive value of 78% for organoid informed treatment, which outperforms response rates observed with empirically guided treatment selection.

Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response

“…Thirdly, in line with previous research showing that bias caused by the proliferation rate of PDOs can be avoided by using GR metrics for organoid response analysis [ 32 ], we confirm that using GR metrics improved the correlation with patient response. Despite good correlations of PDO and clinical response in studies employing both percentage viability and GR metrics [ 6 , 7 ], we found that GR metrics showed better correlation with patient response than percentage viability metrics. Previous studies used DRC parameters AUC, IC 50 , GR 50 or GR max to evaluate organoid response [ 14 – 16 , 23 ].…”

“…Regarding the correlation of PDO response with clinical response, our findings are in line with previous results. In a recent systematic review the overall positive predictive value for organoid informed treatment for CRC is 68% and the negative predictive value is 78% for standard of care chemotherapy, targeted therapy and radiotherapy [ 6 ]. In literature, consistent results are seen for 5-FU and irinotecan-based treatment, showing good correlations of the AUC with both RECIST response and PFS in several, relatively small, studies which align with our results [ 6 , 7 , 14 – 16 , 23 ].…”

“…A promising predictive biomarker is in vitro response testing using patient-derived organoids (PDOs) [ 6 , 7 ]. PDOs are (cancer) stem-cell derived, 3D self-organizing and proliferating structures comprised of epithelial cells representing their corresponding tumour genomically and phenotypically and are well suited for (high throughput) drug screening [ 7 – 11 ].…”

“…However, these results are not consistent, especially not for oxaliplatin which is one of the main treatments for mCRC [ 20 , 23 ]. Variation between studies arise by using different combination screen set-ups, different response evaluation readouts and differences in components used in the screening medium [ 6 , 7 , 20 , 24 – 26 ]. Especially the use of N-acetyl cysteine (NAC) in organoid culture media is point of debate [ 11 ].…”

Human intestinal organoids: Modeling gastrointestinal physiology and immunopathology — current applications and limitations

“…Organoids are used to model the various stages of cancer progression from initiation to metastasis [26,27], and to study drivers of colorectal carcinogenesis including chronic inflammation [28]. CRC organoids have been shown to be highly predictive of patient response to anticancer therapies [29], and can be utilized to identify new CRC biomarkers and develop novel treatment strategies for CRC subtypes with poor prognosis [30,31]. Organoid technology has enabled the in vitro study of diverse CRC subtypes and different disease stages; and has the potential to revolutionize drug development and patient treatment.…”