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BACKGROUND A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers. METHODS We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments. RESULTS We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures. CONCLUSION While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers. TRIAL REGISTRATION Not applicable. FUNDING The Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).

105 Background: Screening for cervical cancer with pap smears and HPV testing can improve patient outcomes by allowing for early identification of cervical cancer. The Minnesota Community Measure and Mayo Clinic's goal is to have a cervical cancer screening rate of 82% (Detailed Report-Cervical Cancer Screening, 2020). Healthy People 2030 aims to have a cervical cancer screening rate of 83.4% (Increase the proportion of females who get screened for cervical cancer -C-09, 2021). Community Internal Medicine cervical cancer screening rates are below this level at 63.09% compliance, with 5,239 patients non-compliant, who are eligible for cervical cancer screenings. Olmsted County only offers acute services on the weekends with no primary care services, which leaves women who work during the week or have childcare/caregiver issues with no options on the weekend or evenings when they have availability to attend appointments. Methods: Based on guidelines for pap smear screening (women ages 21-65), 14,195 women were identified within CIM to be eligible for screening. Of those, 5,239 were due for screening. The Saturday Pap Smear Clinic had 88 available spots. We aimed to improve cervical cancer screening rates among non-compliant women within Community Internal Medicine by 1% (52 women, total noncompliant women = 5,239) by January 2021 without adversely impacting coverage of existing clinic hours. Results: The electronic medical record (EMR), EPIC, was utilized to identify all patients who were eligible for a pap smear based on current guidelines (Total eligible = 14,195; Sample size/non-compliant: 5,239 patients) within Community Internal Medicine (CIM) of the Baldwin Building in Rochester, MN. Interventions included: surveys that were sent to patients via the Patient Portal. Advertising for the Saturday Clinic included Primary Care News, E-boards, Posters, Social Media, SCOPE, Mayo News, and Providers. The Saturday clinic allowed time outside the traditional hours. One unique feature of the clinic is that all females staffed it during clinic hours in an attempt to alleviate some of the fear/anxiety. After completion of the pilot Saturday Pap Clinic, pap smear compliance from the Saturday Pap Clinic alone arose 1.2% (62 patients) within CIM. Conclusions: Post-intervention, cervical screening rates among non-compliant women within Baldwin CIM improved by 1.2% (62 women total).

AbstractThe modulation of GLI2, an oncogenic transcription factor commonly upregulated in cancer, is in many cases not due to genetic defects, suggesting dysregulation through alternative mechanisms. The identity of these molecular events remains for the most part unknown. Here, we identified TFII-I as a novel repressor of GLI2 expression. Mapping experiments suggest that the INR region of the GLI2 promoter is necessary for GLI2 repression. ChIP studies showed that TFII-I binds to this INR. TFII-I knockdown decreased the binding of NELF-A, a component of the promoter–proximal pausing complex at this site, and enriched phosphorylated RNAPII serine 2 in the GLI2 gene body. Immunoprecipitation studies demonstrate TFII-I interaction with SPT5, another pausing complex component. TFII-I overexpression antagonized GLI2 induction by TGFβ, a known activator of GLI2 in cancer cells. TGFβ reduced endogenous TFII-I binding to the INR and increased RNAPII SerP2 in the gene body. We demonstrate that this regulatory mechanism is not exclusive of GLI2. TGFβ-induced genes CCR7, TGFβ1 and EGR3 showed similar decreased TFII-I and NELF-A INR binding and increased RNAPII SerP2 in the gene body post-TGFβ treatment. Together these results identify TFII-I as a novel repressor of a subset of TGFβ-responsive genes through the regulation of RNAPII pausing.