Modeling colorectal cancer: A bio‐resource of 50 patient‐derived organoid lines

Abstract

Background and Aim: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. To improve outcomes for these patients, we need to develop new treatment strategies. Personalized cancer medicine, where patients are treated based on the characteristics of their own tumor, has gained significant interest for its promise to improve outcomes and reduce unnecessary side effects. The purpose of this study was to examine the potential utility of patient-derived colorectal cancer organoids (PDCOs) in a personalized cancer medicine setting. Methods: Patient-derived colorectal cancer organoids were derived from tissue obtained from treatment-naïve patients undergoing surgical resection for the treatment of CRC. We examined the recapitulation of key histopathological, molecular, and phenotypic characteristics of the primary tumor. Results:We created a bio-resource of PDCOs from primary and metastatic CRCs. Key histopathological features were retained in PDCOs when compared with the primary tumor. Additionally, a cohort of 12 PDCOs, and their corresponding primary tumors and normal sample, were characterized through whole exome sequencing and somatic variant calling. These PDCOs exhibited a high level of concordance in key driver mutations when compared with the primary tumor. Conclusions: Patient-derived colorectal cancer organoids recapitulate characteristics of the tissue from which they are derived and are a powerful tool for cancer research. Further research will determine their utility for predicting patient outcomes in a personalized cancer medicine setting.

Renin–Angiotensin Inhibitor, Captopril, Attenuates Growth of Patient-Derived Colorectal Liver Metastasis Organoids

“…On the other hand, “normal” liver organoids were successfully established from all 17 patients. It may seem counterintuitive that non-cancerous liver PDOs are easier to grow than CRLM PDOs, however, challenges with CRC culture have also been experienced by others in the field [ 31 ], indicating a lack of laboratory-to-laboratory standardization of protocols.…”

Applications for Colon Organoid Models in Cancer Research

“…It is typical to record patient demographics including the age, gender, ethnicity, and family history, as well as medical history, comorbidities, medications, and previous treatments, and to investigate and report on information such as clinical phenotype, histological and pathological reports, and molecular profiling (genetic, epigenetic, proteomic, etc.) [23,[45][46][47][48][49]. Access to a biobank reduces the time and resources required for researchers to populate a study.…”

“…Organoid biobanks are a useful source of material for performing drug screening, particularly when deriving patient-matched normal colon and colon tumour organoids. Colon organoid biobanks or libraries have previously been established, described, characterised, and reviewed [23,41,[45][46][47][48]. In 2015, van der Wetering et al reported on the establishment of an organoid library consisting of 22 tumour organoids and 19 normal colon organoids from 20 individual patients, with the samples displaying variation in their growth success ranging from a yield of 10-20 organoids to thousands of organoids [47].…”

Human Intestinal Organoids and Microphysiological Systems for Modeling Radiotoxicity and Assessing Radioprotective Agents

“…They can be co-cultured with immune cells to give a better microenvironment representation [124]. To mimic the responses of patients to treatment-induced toxicity [125][126][127][128][129], patient-derived tumor organoids (PDTOs) [130] can be used to provide an improved model to study the effects of irradiation on colorectal tissue and gut microbiota (Figure 3). With radiotherapy and PDTOs being an increasing focus of studies since 2018 [131], multiple models derived from rectal cancer patients undergoing radiotherapy have been implemented to understand resistance mechanisms to treatment, predict treatment outcomes, and evaluate new adjuvant treatment strategies, including food supplements [128,129,[132][133][134].…”