Browsing by Author "Kuc, Kornelia"

Colorectal cancer (CRC) is the second deadliest cancer in the world. Given the heterogeneity of the disease, a substantial percentage of patients do not benefit from the standard-of-care. The ability to identify patients that most or least likely to respond to the generic therapy prior to its implementation would improve the safety and efficacy of the anti-cancer regimen in CRC.The goal of this study was to assess the suitability of patient-derived organoids (PDOs) as in vitro models to evaluate the efficacy of chemotherapy in CRC. PDOs were generated from surgical tumor specimens of rectal cancer patients. Next, PDOs were treated with standard of care chemotherapeutics for rectal cancer, with or without neoadjuvant radiotherapy, and a commercial cell viability assay was used to assess drug response. PDOs were classified according to the consensus molecular subtype (CMS) system, based on the whole transcriptome sequencing of PDO-derived RNA before treatment. Clinical information was retrieved from the patient records. In vitro drug responses of PDOs revealed heterogeneous drug sensitivity profiles and highlighted patients who would benefit from standard of care. With respect to the consensus molecular subtype (CMS) classification, CMS2 organoids showed highest response to standard of care, while CMS1 PDOs exhibited a less responsive phenotype. For the majority of the PDOs, neoadjuvant radiotherapy prior to drug treatment had no effect on drug response. On the other hand, in certain cases, neoadjuvant therapy sensitized or desensitized PDOs to standard of care chemotherapeutics. This study adds to the literature demonstrating the feasibility of PDOs as platforms for modelling cancer treatment and highlighting their potential to facilitate progress in personalized medicine. More studies involving complex, co-culture PDO models and designed to better reflect the relevant interplay between tumor microenvironment and the anti-cancer regimen are needed to confirm the predictive qualities of the PDOs and inform clinical decisions in CRC.