Details

Autor(en) / Beteiligte

• Cho, Young‐Won
• Min, Dong‐Wook
• Kim, Hwang‐Phill
• An, Yohan
• Kim, Sheehyun
• Youk, Jeonghwan
• Chun, Jaeyoung
• Im, Jong Pil
• Song, Sang‐Hyun
• Ju, Young Seok
• Han, Sae‐Won
• Park, Kyu Joo
• Kim, Tae‐You

Titel

Patient‐derived organoids as a preclinical platform for precision medicine in colorectal cancer

Ist Teil von

• Molecular oncology, 2022-06, Vol.16 (12), p.2396-2412

Ort / Verlag

United States: John Wiley & Sons, Inc

Erscheinungsjahr

2022

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Patient‐derived organoids are being considered as models that can help guide personalized therapy through in vitro anticancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole‐exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an ‘organoid score’ based on the variable anticancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard‐of‐care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression‐free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA‐approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anticancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients. Patient‐derived organoids (PDOs) represent valuable ex vivo models in evaluating personalized therapeutic options. Here, we demonstrated that organoid score, calculated according to organoid response to drugs prescribed to the matched patient, can be predictive of disease progression in patients with colorectal cancer. We also evaluated additional therapeutic options by in vitro drug library screening of FDA‐approved drugs in PDOs. Our data suggest that PDOs could be used for the preclinical evaluation of off‐label therapeutics in patients with cancer.