Use of Patient-Derived Organoids as a Treatment Selection Model for Colorectal Cancer:A Narrative Review

SIMPLE SUMMARY: Colorectal cancer (CRC) is the third most common type of cancer globally. Despite successful treatment, it has a 40% chance of recurrence within five years after surgery. While neoadjuvant chemotherapy is offered for stage IV cancers, it comes with a risk of resistance and disease progression. CRC tumors vary biologically, recur frequently, and pose a significant risk for cancer-related mortality, making it increasingly relevant to develop methods to study personalized treatment. A tumor organoid is a miniature, multicellular, and 3D replica of a tumor in vitro that retains its characteristics. Here, we discuss the current methods of culturing organoids and the correlation of drug response in organoids with clinical responses in patients. This helps us to determine whether organoids can be used for treatment selection in a clinical setting. Based on the studies included, there was a strong correlation between treatment responses of organoids and clinical treatment responses. ABSTRACT: Surgical resection is the mainstay in intended curative treatment of colorectal cancer (CRC) and may be accompanied by adjuvant chemotherapy. However, 40% of the patients experience recurrence within five years of treatment, highlighting the importance of improved, personalized treatment options. Monolayer cell cultures and murine models, which are generally used to study the biology of CRC, are associated with certain drawbacks; hence, the use of organoids has been emerging. Organoids obtained from tumors display similar genotypic and phenotypic characteristics, making them ideal for investigating individualized treatment strategies and for integration as a core platform to be used in prediction models. Here, we review studies correlating the clinical response in patients with CRC with the therapeutic response in patient-derived organoids (PDO), as well as the limitations and potentials of this model. The studies outlined in this review reported strong associations between treatment responses in the PDO model and clinical treatment responses. However, as PDOs lack the tumor microenvironment, they do not genuinely account for certain crucial characteristics that influence therapeutic response. To this end, we reviewed studies investigating PDOs co-cultured with tumor-infiltrating lymphocytes. This model is a promising method allowing evaluation of patient-specific tumors and selection of personalized therapies. Standardized methodologies must be implemented to reach a “gold standard” for validating the use of this model in larger cohorts of patients. The introduction of this approach to a clinical scenario directing neoadjuvant treatment and in other curative and palliative treatment strategies holds incredible potential for improving personalized treatment and its outcomes

The temporal evolution of histological abnormalities in microscopic colitis

BACKGROUND AND AIMS: Microscopic colitis (MC) is a common cause of chronic watery diarrhoea but long-term follow-up data are sparse. METHODS: We performed a retrospective review of health records and all pathology reports in a regional cohort of patients with MC to describe the change in pre- and post-diagnostic colon biopsies. RESULTS: MC was diagnosed in 468 patients with collagenous colitis (CC), 361 with lymphocytic colitis (LC) and 226 with incomplete MC (MCi). The 2014 incidence of CC, LC and MCi was 14.5, 14.9 and 5 per 10(5). Biopsies from both right and left colon were obtained in 237 (51%) patients with CC, 200 (55%) with LC and 107 (47%) with MCi. The diagnostic sensitivities of both left- and right-sided biopsies for MC were high and did not differ. Pre-diagnostic biopsies were obtained in 150 patients and lamina propria inflammation was described in 59, 47 and 43% of patients with a diagnosis of CC, LC and MCi respectively within 1 year, while histology was normal in 16, 13 and 21%. Post-diagnostic biopsies were obtained in 283 patients. MC persisted for up to one year in 77% with CC, 64% with LC and 45% with MCi, of whom 6, 9 and 18% respectively changed to a different MC subgroup. CONCLUSIONS: Colonic biopsies obtained prior to the MC diagnosis often revealed increased lamina propria inflammation. The pathological changes of CC and LC are more persistent than those of MCi. Biopsies from the descending or sigmoid colon are sufficient to elucidate whether a patient with chronic watery diarrhoea has MC