Colorectal cancer (CRC) represents the third most frequently diagnosed malignancy worldwide and is the second most common cause of tumor-associated mortalities in Korea. Due to the disease's aggressive behavior, the 5-year survival rate for CRC patients remains unpromising. Well-characterized cell lines have been used as a biological model for studying the biology of cancer and developing novel therapeutics. To assist in vitro studies, 18 CRC cell lines () derived from Korean patients were established and characterized in the present study. General characteristics of each cell line including doubling time, in vitro morphology, mutational profiles, and protein expressions of CRCrelated genes were described. Whole exome sequencing was performed on each cell line to configure mutational profiles. Single nucleotide variation, frame shift, in-frame deletions and insertions, start codon deletion, and splice stop codon mutation of various genes were found and classified based on their pathogenicity reports. In addition, cell viability was assayed to measure their sensitivities to 24 anti-cancer drugs including anti-metabolites, kinase inhibitors, histone deacetylase inhibitors, alkylating inhibitors, and topoisomerase inhibitors, all widely used for various cancers. On testing, five CRC cell lines showed MSI, of which MLH1 or MSH6 gene was mutated. These newly established CRC cell lines can be used to investigate biological characteristics of CRC, particularly for investigating gene alterations associated with CRC.Colorectal cancer (CRC) represents the third most frequently diagnosed tumor worldwide and is the second most common cause of tumor-associated mortalities in Korea 1,2 . It remains the second most perpetual type of tumor in both genders (men: 12.4%; women: 10.1%), and the number of CRC cases continues to increase. Approximately 25% of CRC cases are diagnosed in stage IV, and recurrence with distance metastasis follows after primary resection in nearly 50% of CRC patients 3 . Due to its aggressive behavior, the 5-year relative survival rate remains disapproving 4 . Neoadjuvent therapy is generally performed before surgical resection as single-or multi-agent chemotherapy to improve prognosis 5 . While roughly 50% of CRC patients respond to customary chemotherapy, the majority develop drug resistance through the course of treatment, and relapse or distance metastasis often follows. In recent years, novel anti-cancer agents that target surface growth factor receptors have been developed as adjuvant therapy to decrease the risk of the cancer recurrence 6 .Well-characterized cell lines have been used as models for studying the biology of cancer and developing novel therapeutics 7 . However, most of the widely used CRC cell lines were derived from Caucasian and African American populations. Accordingly, inter-heterogeneity from ethnic diversity has been biased toward Western countries. To address this need, we established and characterized 18 novel CRC cell cultures
Multifocal colorectal cancer (CRC) comprises both clonally independent primary tumors caused by inherited predisposition and clonally related tumors mainly due to intraluminal spreading along an intact basement membrane. The distinction between these multifocal CRCs is essential because therapeutic strategies vary according to the clonal association of multiple tumor masses. Here, we report one unique case of synchronous intestinal cancer (SIC) with tumors occurring along the entire bowel tract, including the small intestine. We established six patient-derived organoids (PDOs), and patient-derived cell lines (PDCs) from each site of the SIC, which were subjected to extensive genomic, transcriptomic, and epigenomic sequencing. We also estimated the drug responses of each multifocal SIC to 25 clinically relevant therapeutic compounds to validate how the clinically actionable alternations between SICs were associated with drug sensitivity. Our data demonstrated distinct clonal associations across different organs, which were consistently supported by multi-omics analysis, as well as the accordant responses to various therapeutic compounds. Our results indicated the imminent drawback of a single tumor-based diagnosis of multifocal CRC and suggested the necessity of an in-depth molecular analysis of all tumor regions to avoid unexpected resistance to the currently available targeted therapies.
Gastrointestinal cancer accounts for one-third of the overall cancer occurrence worldwide. Pancreatic ductal adenocarcinoma (PDAC) is a type of gastrointestinal cancer that is known to be one of the most fatal among all cancer types, with a 5-year survival rate of less than 8%. Chemotherapy combined with surgical resection is its probable curative option. However, surgery is accessible for only 10-15% of patients diagnosed with PDAC. Organoids show self-organizing capacities and resemble the original tissue in terms of morphology and function. Organoids can also be cultured with high effectiveness from tumor tissues derived from each patient, making them an extremely fitting model for translational uses and improving personalized cancer medicine. Enhancing drug screening platforms is necessary to apply personalized medicinebased organoids in clinical settings.
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